Tbio MLST8 Target of rapamycin complex subunit LST8

Protein Summary

Description

Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity. In nutrient-poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'.

Uniprot Accession IDs

• Q9BVC4
• B3KMM4
• B4DY00
• D3DU88
• Q5M800
• Q86Y18
• Q8WUI5
• Q9HA66
• Q9UJV6
• TORC subunit LST8

Gene Name

• MLST8

Ensembl ID

• ENST00000382450
• ENSP00000371888
• ENSG00000167965
• ENST00000397124
• ENSP00000380313
• ENST00000564088
• ENSP00000457870
• ENST00000565250
• ENSP00000455046
• ENST00000569417
• ENSP00000456405

Symbol

• GBL
• LST8
• GBL
• LST8
• POP3
• WAT1
• GbetaL

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	0.85
protein domain	0.85
pathway	0.76
transcription factor	0.69
transcription factor binding site profile	0.69

Protein Classes

No PANTHER Classes or DTO Classes found

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: 282.93   (req: < 5)

Gene RIFs: 16   (req: <= 3)

Antibodies: 447   (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: 282.93   (req: >= 5)

Gene RIFs: 16   (req: > 3)

Antibodies: 447   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 12

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