Tbio EIF4B Eukaryotic translation initiation factor 4B

Protein Summary

Description

Required for the binding of mRNA to ribosomes. Functions in close association with EIF4-F and EIF4-A. Binds near the 5'-terminal cap of mRNA in presence of EIF-4F and ATP. Promotes the ATPase activity and the ATP-dependent RNA unwinding activity of both EIF4-A and EIF4-F.

Uniprot Accession IDs

• P23588
• B4DS13
• Q4G0E3
• Q53HQ2
• Q6GPH5
• Q6IB46
• Q8WYK5
• eIF-4B

Gene Name

• EIF4B

Ensembl ID

• ENST00000262056
• ENSP00000262056
• ENSG00000063046
• ENST00000416762
• ENSP00000412530

Symbol

• EIF-4B
• PRO1843

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
drug perturbation	1
transcription factor perturbation	1
disease perturbation	0.99
kinase perturbation	0.99
interacting protein	0.98

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Rna Binding Protein / Translation Factor / Translation Initiation Factor / Eukaryotic Translation Initiation Factor 4b

DTO Classes

Protein / Nucleic Acid Binding / Rna Binding Protein / Translation Factor / Translation Initiation Factor / Eukaryotic Translation Initiation Factor 4b

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 141.09   (req: < 5)

Gene RIFs: 30   (req: <= 3)

Antibodies: 757   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 141.09   (req: >= 5)

Gene RIFs: 30   (req: > 3)

Antibodies: 757   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 10

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (277 Tissues)

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Circle Plot (2)

Anatomogram

root: immaterial entity (BFO:0000141)

root: material entity (BFO:0000040)

Coexpression Data

Tissue Specific Coexpression (640)

Illuminating Dark Proteins using Reactome Pathways.

Brunson et al., bioRxiv : the preprint server for biology, 2023-06-05

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Coexpressed Target

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EIF3L 28

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IGBP1 22

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EIF3E 22

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PABPC1 17

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PCBP2 16

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EEF1A1 14

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CAMLG 12

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ST13 12

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NPM1 12

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CCNI 11

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EIF3H 11

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SYF2 11

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CCNG1 10

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ZNF277 9

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EIF3D 9

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TOMM20 9

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EIF3F 8

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LTA4H 8

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RSL24D1 8

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RPL5 7

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EIF2S3 7

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NAP1L1 7

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MRPL45 7

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RPL22 6

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RPL15 5

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RPL4 5

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RPL7 5

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BTF3 5

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NSA2 5

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FXR1 5

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NOA1 5

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EEF2 5

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RSL1D1 5

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MKRN1 4

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RPL3 4

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NACA 4

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EIF2A 4

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COPS2 4

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FAM175A 4

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DYM 4

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THG1L 4

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CSNK2A2 4

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NONO 4

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KIAA0430 4

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CSDE1 4

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POLR1D 4

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RPS3A 3

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RPL6 3

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RPL31 3

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COX7A2L 3

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RPL23A 3

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RPS13 3

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LETMD1 3

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DHX40 3

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RPL7A 3

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HNRNPA1 3

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IPO5 3

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POLR1E 3

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ANP32B 3

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EIF4A2 2

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CREBL2 2

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RPS4X 2

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PMPCB 2

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RPS27A 2

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YTHDC1 2

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TFDP2 2

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TMEM192 2

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JAK1 2

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CDK19 2

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RACK1 2

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EEF1G 2

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RPS15A 2

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EIF2D 2

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RPS3 2

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CTSF 2

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RPL14 2

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RPL17 2

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RPL11 2

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RPL29 2

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RPL26 2

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RPL23 2

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RPL21 2

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RPL35A 2

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RPL32 2

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RPL30 2

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CCNB1IP1 2

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GLTSCR2 2

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RPS20 2

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RPS27 2

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RPS25 2

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MMGT1 2

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EIF3M 2

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KDELR1 2

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CRTAP 2

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ABCB7 2

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ZFAND1 2

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ELP2 2

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RAB4A 1

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RPL36AL 1

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PHF3 1

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MXI1 1

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QARS 1

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WASF2 1

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GGA2 1

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WBP11 1

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NIPAL3 1

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PDXDC1 1

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MAPRE2 1

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CYB5B 1

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MRPS27 1

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MCPH1 1

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PRPS1 1

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ELK4 1

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NFATC2IP 1

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ESYT2 1

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UBE2G2 1

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RBBP7 1

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SET 1

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PRKRA 1

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RFX5 1

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HNRNPH1 1

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TRIM44 1

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AKT3 1

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URI1 1

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DAP3 1

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PHF10 1

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PABPC4 1

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QRICH1 1

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KDM2B 1

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PTDSS1 1

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MPRIP 1

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EEF2K 1

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CS 1

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TPP2 1

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RBMX 1

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NFX1 1

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DCTD 1

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PJA1 1

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WWP1 1

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DLST 1

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TTC3 1

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TIMM10B 1

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MAP3K4 1

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R3HDM1 1

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TYW1 1

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TULP4 1

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RPL13A 1

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UBXN1 1

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TTF1 1

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MAP2K5 1

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ZNF581 1

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FOXO4 1

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CNBP 1

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RPS6 1

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FBXO7 1

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BFAR 1

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UPF2 1

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CCDC28A 1

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MRPL10 1

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SAV1 1

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RPS11 1

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RPL10A 1

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KIAA1191 1

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TPT1 1

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XRCC5 1

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RPUSD4 1

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PPP1CC 1

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BCL2L13 1

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MMADHC 1

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EIF3A 1

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VDAC2 1

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NMD3 1

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GMPS 1

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OLA1 1

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GDI2 1

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NCOA4 1

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SERBP1 1

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PLAA 1

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CCT4 1

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UBE4B 1

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UQCRC2 1

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MRPL30 1

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KARS 1

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NOB1 1

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PPP6C 1

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METAP2 1

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TXNDC16 1

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SELENOP 1

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ARMCX1 1

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AMFR 1

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G3BP2 1

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NUCKS1 1

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RBSN 1

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SCAPER 1

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CCDC47 1

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PHF20 1

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SERINC1 1

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SLC39A6 1

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ATP9A 1

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RRM1 1

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SCARB2 1

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FBXW11 1

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TMEM159 1

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FKBP9 1

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APH1A 1

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MRPL33 1

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SLU7 1

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NBR1 1

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FBXO21 1

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DDX6 1

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RPS8 1

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RPS7 1

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UQCRB 1

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PFDN5 1

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RPL19 1

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TATDN1 1

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RPL24 1

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RPL9 1

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RPL8 1

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RPL38 1

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RPL41 1

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PHB2 1

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TIMM9 1

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EIF3G 1

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CCDC59 1

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DPH5 1

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RPS23 1

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TOMM7 1

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HSP90AB1 1

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C11orf57 1

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TARSL2 1

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RBMX2 1

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SIRT1 1

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STAG2 1

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EZH1 1

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CRBN 1

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TRIM4 1

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OARD1 1

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OXA1L 1

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CIR1 1

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GID8 1

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KIZ 1

Data Source

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GTEx 640

Tissue

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Thyroid 89

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Ovary 82

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WholeBlood 53

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Artery-Tibial 42

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Pancreas 41

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Esophagus-GastroesophagealJunction 35

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Pituitary 32

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Colon-Sigmoid 31

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Brain-Cerebellum 27

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Esophagus-Muscularis 24

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AdrenalGland 22

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Artery-Aorta 21

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Prostate 19

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Uterus 19

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Kidney-Cortex 15

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Cells-Culturedfibroblasts 14

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Adipose-Subcutaneous 10

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Spleen 8

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Esophagus-Mucosa 6

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MinorSalivaryGland 5

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Artery-Coronary 5

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Nerve-Tibial 5

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Heart-AtrialAppendage 5

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Heart-LeftVentricle 5

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Brain-CerebellarHemisphere 4

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Cells-EBV-transformedlymphocytes 4

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Muscle-Skeletal 3

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Brain-Hippocampus 3

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Lung 2

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Liver 2

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Adipose-Visceral-Omentum 2

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Colon-Transverse 1

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Testis 1

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Brain-Spinalcord-cervicalc-1 1

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Skin-NotSunExposed-Suprapubic 1

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Skin-All 1

Items per page:

5

1 – 5 of 640

Coexpressed Target	Data Source	Tissue	No Header
EIF3L	GTEx	Colon-Transverse
EIF3L	GTEx	Lung
IGBP1	GTEx	Lung
CAMLG	GTEx	MinorSalivaryGland
ST13	GTEx	MinorSalivaryGland

Cancer Specific Coexpression (144)

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Coexpressed Target

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EEF1A1 11

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EIF3L 11

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HNRNPA1 4

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EEF2 4

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LETMD1 3

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ABCB7 3

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RPS3A 2

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HBP1 2

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ST13 2

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IGBP1 2

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RSL1D1 2

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TOMM20 2

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EIF2A 2

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ZNF740 2

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RPL6 2

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NACA 2

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NONO 2

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LTA4H 2

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ABRAXAS1 2

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METAP2 2

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IPO5 2

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EIF3A 2

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EEF1B2 2

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NPM1 2

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RFC1 1

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PPP1CC 1

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UHRF1BP1L 1

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WBP11 1

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NUP107 1

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PWP1 1

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NUP37 1

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MAGI3 1

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RPL22 1

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STAG2 1

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KIAA1143 1

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TAF1 1

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SCAF11 1

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POLA1 1

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FOPNL 1

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FAM122B 1

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TWISTNB 1

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KDM3A 1

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SINHCAF 1

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MSI2 1

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FAM169A 1

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ZNF791 1

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ZNF91 1

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ITPR2 1

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SLC38A1 1

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PTGES3 1

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MPP5 1

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CCNT1 1

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PARP8 1

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ATF7 1

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CTDSP2 1

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EIF2S3 1

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CCNI 1

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LRPPRC 1

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MMGT1 1

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CSDE1 1

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IPO7 1

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RPL15 1

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BMP2 1

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FERMT1 1

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FCHSD2 1

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PABPC1 1

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NAP1L1 1

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TCF12 1

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RPL3 1

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RPL4 1

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SIRT1 1

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SOX6 1

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RPL7 1

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EIF3E 1

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EIF3H 1

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MRPL45 1

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RPS23 1

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EIF3F 1

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NOA1 1

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ZNF277 1

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CS 1

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PABPC4 1

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RPL17 1

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RPL41 1

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RABGGTB 1

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RPLP0P6 1

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RPLP0 1

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SARS 1

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PCBP2 1

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RPS12 1

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RPL10A 1

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BTF3 1

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EIF4A2 1

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RBMX 1

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FAM214A 1

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PFKM 1

Data Source

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TCGA 144

Cancer Type

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KICH 38

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LGG 28

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KIRC 14

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ACC 14

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THCA 8

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MESO 8

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PCPG 7

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UCEC 5

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SARC 4

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CHOL 3

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OV 2

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READ 2

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BLCA 2

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CESC 2

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STAD 1

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THYM 1

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HNSC 1

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PRAD 1

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KIRP 1

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BRCA 1

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LIHC 1

Items per page:

5

1 – 5 of 144

Coexpressed Target	Data Source	Cancer Type	No Header
EEF1A1	TCGA	STAD
RFC1	TCGA	KICH
PPP1CC	TCGA	KICH
HNRNPA1	TCGA	KICH
RPS3A	TCGA	KICH

Protein Sequence and Structure

Residue Counts

Protein Sequence

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ProtVista Viewer

Related Tools (5)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Protein-Protein Interactions (353)

Explore Interacting Targets

1 – 10 of 353

• See Interactions on String-DB

RBM12B

Tdark

Novelty:  0.96079205

p_int:  1

Data Source:  BioPlex

NIF3L1

Tbio

Novelty:  0.15581813

p_int:  0.999443417

p_ni:  0.000556583

Data Source:  BioPlex

NCOA5

Tbio

Novelty:  0.09053523

p_int:  0.982891694

p_ni:  0.017078213

p_wrong:  0.000030093

Score:  0.181

Data Source:  BioPlex,STRINGDB

EIF4G1

Tbio

Novelty:  0.00170995

Score:  0.999

Data Source:  Reactome,STRINGDB

EIF4A1

Tchem

Novelty:  0.00269994

Score:  0.999

Data Source:  Reactome,STRINGDB

RPS6

Tbio

Novelty:  0.00122241

Score:  0.998

Data Source:  STRINGDB

EIF4A2

Tbio

Novelty:  0.00298045

Score:  0.998

Data Source:  Reactome,STRINGDB

EIF4E

Tchem

Novelty:  0.00072182

Score:  0.996

Data Source:  Reactome,STRINGDB

EIF3A

Tbio

Novelty:  0.00434615

Score:  0.996

Data Source:  STRINGDB

PABPC1

Tbio

Novelty:  0.00197523

Score:  0.995

Data Source:  Reactome,STRINGDB

Predicted Interactions

Reactome Functional Interactions (FIs) (913)

Illuminating Dark Proteins using Reactome Pathways.

Brunson et al., bioRxiv : the preprint server for biology, 2023-06-05

Explore Targets Download Predictions

FI Score

description

0.50

0.98

[ 0.50, 0.98 ]

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Items per page:

5

1 – 5 of 913

FI Partner	FI Score
EIF3E	0.97
EIF4H	0.96
EIF3H	0.95
EIF3B	0.95
EIF4G1	0.95

Nearest Tclin Targets (1)

Explore Nearest Tclin Targets

Upstream (1)

1 – 1 of 1

MTOR

Tclin

IDG Family:  Kinase

KEGG Distance:  2

Common Pathways:  3

1: PI3K-Akt signaling pathway

2: mTOR signaling pathway

3: Proteoglycans in cancer

Pathways (25)

Reactome (15)

KEGG (4)

PathwayCommons (1)

WikiPathways (5)

Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S (R-HSA-72662)

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Expression Scale

Shows the different values of expression colour coded.

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For selected nodes the values are shown on the right hand side.

The median is flagged in a different colour for nodes with multiple expression values.

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Regulation Scale

Shows the results of the gene set analysis.

Results are shown as five categories: (▲▲) significantly up-regulated, (▲) non-significantly up-regulated, (▼) non-significantly down-regulated, (▼▼) significantly down-regulated, and not (-) found.

For selected nodes the values are shown on the right hand side. The median is flagged in a different colour for nodes with multiple expression values.

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Interactors:

FI Score ≥

fdr ≤

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Converting to Functional Interactions...

No functional interactions available.

Overlay Tool

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Overlay Data

This tool allows you to overlay data on the currently displayed pathway diagram or functional interaction view.

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This tool allows users to overlay pairwise relationship data onto pathway level diagrams and the functional interaction view.

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Find Similar Targets

Items per page:

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1 – 5 of 15

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	61 targets	R-HSA-72662
Reactome	Cap-dependent Translation Initiation	121 targets	R-HSA-72737
Reactome	Deadenylation of mRNA	22 targets	R-HSA-429947
Reactome	Deadenylation-dependent mRNA decay	53 targets	R-HSA-429914
Reactome	Eukaryotic Translation Initiation	121 targets	R-HSA-72613

Name	Explore in Pharos	Explore in Source
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	61 targets	R-HSA-72662
Cap-dependent Translation Initiation	121 targets	R-HSA-72737
Deadenylation of mRNA	22 targets	R-HSA-429947
Deadenylation-dependent mRNA decay	53 targets	R-HSA-429914
Eukaryotic Translation Initiation	121 targets	R-HSA-72613

Interacting Pathways

Reactome is a manually curated, peer reviewed knowledgebase of human biological pathways and processes, available online as an open access resource that can be freely used and distributed by all members of the biological research community. This view of the Reactome database displays the pathways functionally interacting with EIF4B.

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (13)

Functions (5)

Components (3)

Processes (5)

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Items per page:

5

1 – 5 of 5

GO Term	Evidence	Assigned by
RNA binding	Inferred from High Throughput Direct Assay (HDA)	UniProtKB
ribosomal small subunit binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
RNA strand annealing activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
RNA strand-exchange activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
translation initiation factor activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central

Disease Associations (10)

Explore Associated Diseases Find Similar Targets

1 – 10 of 10

cleft lip

JensenLab Experiment TIGA

Explore Disease: cleft lip

JensenLab Experiment TIGA

• Disease ID:  DOID:9296
• Evidence:  MeanRankScore = 36
• Confidence:  1

major depressive disorder

DisGeNET

Explore Disease: major depressive disorder

DisGeNET

• Disease ID:  UMLS:C1269683
• Evidence:  1 PubMed IDs
• score:  0.31
• Source:  PSYGENET

ovarian cancer

Expression Atlas

Explore Disease: ovarian cancer

Expression Atlas

• Disease ID:  DOID:2394
• Log 2 fold change:  -2
• p-value:  0.00000386666089799879

Unipolar Depression

DisGeNET

Explore Disease: Unipolar Depression

DisGeNET

• Disease ID:  UMLS:C0041696
• Evidence:  1 PubMed IDs
• score:  0.3
• Source:  PSYGENET

large cell medulloblastoma

Expression Atlas

Explore Disease: large cell medulloblastoma

Expression Atlas

• Disease ID:  DOID:3857
• Log 2 fold change:  1.1
• p-value:  0.000334895619164181

oligodendroglioma

Expression Atlas

Explore Disease: oligodendroglioma

Expression Atlas

• Disease ID:  DOID:3181
• Log 2 fold change:  1.1
• p-value:  0.0419429226112312

prostate carcinoma

JensenLab Experiment TIGA

Explore Disease: prostate carcinoma

JensenLab Experiment TIGA

• Disease ID:  DOID:10286
• Evidence:  MeanRankScore = 93
• Confidence:  1.9

lung cancer

Expression Atlas

Explore Disease: lung cancer

Expression Atlas

• Disease ID:  DOID:1324
• Log 2 fold change:  1.2
• p-value:  0.00140062543824974

osteosarcoma

Expression Atlas

Explore Disease: osteosarcoma

Expression Atlas

• Disease ID:  DOID:3347
• Log 2 fold change:  -1.014
• p-value:  0.000642027564255001

psoriasis

Expression Atlas

Explore Disease: psoriasis

Expression Atlas

• Disease ID:  DOID:8893
• Log 2 fold change:  -2.1
• p-value:  0.000564017584903011

Predicted Diseases

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root: disease (DOID:4)

GWAS Traits (20)

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
prostate carcinoma	EFO_0001663	3	2	0	1.2	93.4
low density lipoprotein cholesterol measurement	EFO_0004611	3	2	3		66.8
systolic blood pressure	EFO_0006335	2	2	2		60.9
educational attainment	EFO_0011015	1	3	3		58.9
appendicular lean mass	EFO_0004980	1	1	1		57.1

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 5 of 20

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
prostate carcinoma	EFO_0001663	0	1.2	93.4
low density lipoprotein cholesterol measurement	EFO_0004611	3		66.8
systolic blood pressure	EFO_0006335	2		60.9
educational attainment	EFO_0011015	3		58.9
appendicular lean mass	EFO_0004980	1		57.1

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Find similar targets by:

UniProt Keyword Find Similar Targets

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3D-structure
Acetylation
Alternative splicing
Complete proteome
Direct protein sequencing
Initiation factor
Isopeptide bond
Phosphoprotein
Polymorphism
Protein biosynthesis

GWAS Trait Find Similar Targets

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appendicular lean mass
BMI-adjusted hip circumference
body height
cholesterol:total lipids ratio
cholesteryl ester 18:0 measurement
cholesteryl esters:total lipids ratio
cleft lip
Cleft palate
diastolic blood pressure
educational attainment

IDG Resources

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Orthologs (8)

1 – 5 of 8

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Mouse	eukaryotic translation initiation factor 4B	MGI:95304	75705
Rat	eukaryotic translation initiation factor 4B	RGD:1306479	300253
Dog	eukaryotic translation initiation factor 4B	VGNC:40282	477600
Horse	eukaryotic translation initiation factor 4B	VGNC:17501	100061920
Cow	eukaryotic translation initiation factor 4B	VGNC:28407	505850

Species	Name	OMA	EggNOG	Inparanoid
Mouse	eukaryotic translation initiation factor 4B
Rat	eukaryotic translation initiation factor 4B
Dog	eukaryotic translation initiation factor 4B
Horse	eukaryotic translation initiation factor 4B
Cow	eukaryotic translation initiation factor 4B

Publication Statistics

PubMed Score 141.09

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PubTator Score 107.07

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Publications (53)

Overrepresented Terms from Abstracts

100 terms from up to 100 abstracts, scaled based on the degree of overrepresentation (Fisher's Exact Test p-Value).

PublicationsGeneRIFs

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Backbone resonance assignments of the C-terminal region of human translation initiation factor eIF4B.

Mondal et al., Biomolecular NMR assignments, 2023-12

Abstract: (show)

Translation initiation in eukaryotes is an early step in protein synthesis, requiring multiple factors to recruit the ribosomal small subunit to the mRNA 5' untranslated region. One such protein factor is the eukaryotic translation initiation factor 4B (eIF4B), which increases the activity of the eIF4A RNA helicase, and is linked to cell survival and proliferation. We report here the protein backbone chemical shift assignments corresponding to the C-terminal 279 residues of human eIF4B. Analysis of the chemical shift values identifies one main helical region in the area previously linked to RNA binding, and confirms that the overall C-terminal region is intrinsically disordered.

DOCK3-Associated Neurodevelopmental Disorder-Clinical Features and Molecular Basis.

Matthew S Alexander, Milen Velinov, Genes, 2023-10-14

Abstract: (show)

The protein product of DOCK3 is highly expressed in neurons and has a role in cell adhesion and neuronal outgrowth through its interaction with the actin cytoskeleton and key cell signaling molecules. The DOCK3 protein is essential for normal cell growth and migration. Biallelic variants in DOCK3 associated with complete or partial loss of function of the gene were recently reported in six patients with intellectual disability and muscle hypotonia. Only one of the reported patients had congenital malformations outside of the CNS. Further studies are necessary to better determine the prevalence of DOCK3-associated neurodevelopmental disorders and the frequency of non-CNS clinical manifestations in these patients. Since deficiency of the DOCK3 protein product is now an established pathway of this neurodevelopmental condition, supplementing the deficient gene product using a gene therapy approach may be an efficient treatment strategy.

CDKN2AIP-induced cell senescence and apoptosis of testicular seminoma are associated with CARM1 and eIF4β.

Cao et al., Acta biochimica et biophysica Sinica, 2022-05-25

Abstract: (show)

Testicular seminoma is a relatively rare tumor which is mostly detected in male population aged from 15 to 35 years old. Although several molecular biomarkers have been identified to be associated with testicular seminoma pathogenesis, the exact mechanism for testicular seminoma progression remains largely unknown. CDKN2A interacting protein (CDKN2AIP) has previously been identified as a tumor suppressor in multiple malignant diseases. In this study, we aimed to further explore its role in testicular seminoma as well as the underlying molecular mechanisms. Retrospective testicular seminoma clinical samples, normal tissues, NTERA-2 cell line, and mouse xenograft models were used in this study. RT-qPCR, western blot analysis, immunofluorescence microscopy, Co-IP and IP-MS experiments were performed to detect the expression of CDKN2AIP and its interaction with CARM1 and eIF4β. SA-β-gal staining assay and H3K9me3 activity experiments were used to subsequently evaluate the cell senescence and apoptosis. Mouse xenograft animal model was used for in vivo study. The results showed that CDKN2AIP is highly expressed in normal testis samples, and is significantly suppressed in testicular seminoma clinical samples and cell line model. Up-regulation of CDKN2AIP is significantly associated with the inhibition of testicular seminoma tumor growth and the increase of cell senescence and apoptosis. CDKN2AIP exhibits anti-tumor activity by interacting with CARM1 and eIF4β. CDKN2AIP induces testicular seminoma cell senescence by suppressing CARM1 expression and eIF4β phosphorylation. The CDKN2AIP-CARM1 and CDKN2AIP-eIF4β interactions, which induce tumor cell senescence and apoptosis, may be the potential druggable molecular pathways in testicular seminoma tumor pathogenesis and progression.

eIF4B enhances ATF4 expression and contributes to cellular adaptation to asparagine limitation in BRAF-mutated A375 melanoma.

Iwao et al., Biochemical and biophysical research communications, 2021-10-08

Abstract: (show)

ATF4 is a crucial transcription factor in the integrated stress response, a major adaptive signaling pathway activated by tumor microenvironment and therapeutic stresses. BRAF inhibitors, such as vemurafenib, induce ATF4 in BRAF-mutated melanoma cells, but the mechanisms of ATF4 induction are not fully elucidated. Here, we show that ATF4 expression can be upregulated by eukaryotic initiation factor 4B (eIF4B) in BRAF-mutated A375 cells. Indeed, eIF4B knockout (KO) prevented ATF4 induction and activation of the uORF-mediated ATF4 translation mechanism during vemurafenib treatment, which were effectively recovered by the rescue of eIF4B. Transcriptome analysis revealed that eIF4B KO selectively influenced ATF4-target gene expression among the overall gene expression changed by vemurafenib. Interestingly, eIF4B supported cellular proliferation under asparagine-limited conditions, possibly through the eIF4B-ATF4 pathway. Our findings indicate that eIF4B can regulate ATF4 expression, thereby contributing to cellular stress adaptation, which could be targeted as a therapeutic approach against malignancies, including melanoma.

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

Haenig et al., Cell reports, 2020-08-18

Abstract: (show)

Interactome maps are valuable resources to elucidate protein function and disease mechanisms. Here, we report on an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins and integration of literature interactions. This network reveals interconnectivity across diseases and links many known ND-causing proteins, such as α-synuclein, TDP-43, and ATXN1, to a host of proteins previously unrelated to NDs. It facilitates the identification of interacting proteins that significantly influence mutant TDP-43 and HTT toxicity in transgenic flies, as well as of ARF-GEP100 that controls misfolding and aggregation of multiple ND-causing proteins in experimental model systems. Furthermore, it enables the prediction of ND-specific subnetworks and the identification of proteins, such as ATXN1 and MKL1, that are abnormally aggregated in postmortem brains of Alzheimer's disease patients, suggesting widespread protein aggregation in NDs.