Property Summary

NCBI Gene PubMed Count 66
PubMed Score 229.38
PubTator Score 152.18

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (3)

MLP Assay (1)

AID Type Active / Inconclusive / Inactive Description
651908 confirmatory 0 / 0 / 1 ML327 E-Cadherin HDAC Spectrum Assay_HDAC8

Gene RIF (51)

PMID Text
26923266 Studies indicate that histone deacetylase 8 protein (HDAC8) aberrantly deacetylates p53 protein and promotes leukemia stem cells (LSCs) transformation and maintenance.
26806311 The H143A and H142A/H143A mutants exhibit activity that is >80000-fold lower than that of wild-type HDAC8; the buried D176N and D176A mutants have significant catalytic effects, with more subtle effects caused by D183N and D183A
26792731 cAMP signaling increases HDAC8 protein levels by reducing JNK-mediated autophagy and ubiquitin-proteasome-dependent degradation of the HDAC8 protein in H1299 lung cancer cells.
26463496 Report the preparation and biophysical evaluation of five HDAC8 mutants: P91L, G117E, H180R, D233G, and G304R. Additionally, the double mutants D233G-Y306F and P91L-Y306F were prepared to enable cocrystallization of intact enzyme-substrate complexes.
26412386 Our data exhibited an important role of HDAC8 in promoting gastric cancer tumorigenesis and identify this HDAC8 as a potential therapeutic target for the treatment of gastric cancer.
26402585 Results provide direct evidence that potential KDAC8 substrates can be directly deacetylated by KDAC8.
26387755 study elucidates an HDAC8-mediated p53-inactivating mechanism promoting leukemia stem cells activity
26383163 findings show how HDAC8 drives nonalcoholic fatty liver disease-associated hepatocarcinogenesis
26200462 HDAC8i induced cell growth inhibition and marked S-phase cell cycle arrest in human and murine-derived MPNST cells
25836739 HDAC8 was increased in BRAF-mutated melanoma. Increased cytoplasmic HDAC8 immunoreactivity was independently associated with an improved survival from both diagnosis of primary melanoma and from first detection of stage IV disease to melanoma death
25793284 report the X-ray crystal structures of HDAC8 complexed with three synthetic analogues of Largazole in which the depsipeptide ester is replaced with a rigid amide linkage
25605725 Our mechanistic and cellular studies on HDAC8 activation have the potential to provide insight into the development of novel anticancer drugs.
25516458 Studied the kinetics, thermodynamics, and selectivity of Zn(II) and Fe(II) binding to HDAC8.
25504627 Data reveal a role for miR-21-3p in regulating HDAC8 expression and Akt/Gsk3beta pathway in cardiac hypertrophy.
25451941 histone deacetylase 8 inhibition reduces gene expression and production of proinflammatory cytokines in vitro and in vivo
25407689 detailed thermodynamic studies of the binding of structurally similar ligands, which differed with respect to the "cap", "linker", and "metal-binding" regions of the suberoylanilide hydroxamic acid pharmacophore, to HDAC8
25321483 On the corresponding BMF gene promoter, loss of HDAC8 was associated with signal transducer and activator of transcription 3 (STAT3)/specificity protein 3 (Sp3) transcription factor exchange and recruitment of p300.
25075551 HDAC8 X-ray crystal structures reveal that each Cornelia de Lange syndrome mutation causes local structural changes that compromise catalysis and/or thermostability.
25011684 Deregulation of HDAC8 is frequent in urothelial cancer, but neither specific pharmacological inhibition nor siRNA-mediated knockdown of HDAC8 impaired viability of urothelial cancer cell lines in a therapeutic useful manner.
24920679 In response to contractile stimulation, HDAC8 may mediate cortactin deacetylation, which subsequently promotes actin filament polymerization and smooth muscle contraction.
24404147 DEC1 coordinates with HDAC8 to differentially regulate TAp73 and DeltaNp73 expression.
24403048 Loss-of-function mutations in HDAC8 cause a range of overlapping phenotypic spectrum of Cornelia de Lange syndrome-like feature.
24171457 Using molecular dynamics simulations the study found a mechanism whereby the interactions and dynamics of two loops tune the configuration of functionally important residues of HDAC8 and could therefore influence the activity of the enzyme.
24077923 HDAC8 isoverexpressed in hepatocellular carcinoma; knockdown suppresses tumor growth and enhances apoptosis
23482931 SOX4 is a direct target gene of FRA-2 and induces expression of HDAC8 in adult T-cell leukemia/lymphoma.
23430957 HDAC8 plays an important role in the modulation of SOCS1 and SOCS3 by curcumin.
23111066 Data indicate that knockdown of HDAC8 resulted in the increased expression of SOCS1 and SOCS3, and overexpression of SOCS1 and SOCS3 significantly inhibited cell growth and suppressed JAK2/STAT signaling.
22944197 Data indicate prominent changes in urothelial cancer cell lines (UCC) were HDAC2 and/or HDAC8 up-regulation.
22889856 This family study showa that HDAC8 is involved in a syndromic form of intellectual disability.
22885700 loss of HDAC8 activity results in increased SMC3 acetylation and inefficient dissolution of the 'used' cohesin complex released from chromatin in both prophase and anaphase
22391568 our data uncover a regulatory mechanism of mutant p53 transcription via HDAC8
22046129 Histone deacetylase 8 is required for centrosome cohesion and influenza A virus entry.
21790156 Presented is the 2.14 A-resolution crystal structure of the HDAC8-largazole thiol complex.
21455583 overexpression of HDAC1, 6 or 8 increased invasion and MMP-9 expression in breast cancer cells
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20545365 HDAC8 could bind either or both Fe(2+) or Zn(2+) in vivo.
20029090 it is likely that potassium is the predominant monovalent cations bound to HDAC8 in vivo.
19913121 Observational study of gene-disease association. (HuGE Navigator)
19355988 recent developments in the crystal structure analysis of human HDAC4, HDAC7, and HDAC8 recent developments in the crystal structure analysis of human HDAC4, HDAC7, and HDAC8 [REVIEW]
19118036 Our data point toward an important role of HDAC8 in neuroblastoma pathogenesis
19070599 Expression of recombinant HDAC8 results in decreased CREB activation and CREB mediated gene transcription in response to forskolin application.
19053282 analysis of human histone deacetylase 8 and its site-specific variants complexed with substrate and inhibitors
18256683 HDAC8-selective inhibitors have a unique mechanism of action involving PLCgamma1 activation and calcium-induced apoptosis
17786334 High expression of HDAC8 is associated with cancer tissues
17721440 The crucial role of Asp 101 in substrate and inhibitor recognition was confirmed by activity and binding assays of wild-type HDAC8 and Asp101Ala, Tyr306Phe and Asp101Ala/Tyr306Phe mutants.
16809764 HDAC8 regulation of hEST1B protein stability modulates total telomerase enzymatic activity
16681389 Identification of the in vivo metal ion of HDAC8 is essential for understanding the biological function and regulation of HDAC8 and for the development of improved inhibitors of this class of enzymes
15772115 findings indicate that histone deacetylase 8(HDAC8) associates with the smooth muscle actin cytoskeleton and may regulate the contractile capacity of smooth muscle cells
15590418 The HDAC8, another class I HDAC, was not detected in epithelial cells but was uniquely expressed in the cytoplasm of stromal cells.
15477595 crystal structure
14701748 PKA-mediated phosphorylation of HDAC8 plays a central role in the overall acetylation status of histones.

AA Sequence

MEEPEEPADSGQSLVPVYIYSPEYVSMCDSLAKIPKRASMVHSLIEAYALHKQMRIVKPKVASMEEMATF      1 - 70
HTDAYLQHLQKVSQEGDDDHPDSIEYGLGYDCPATEGIFDYAAAIGGATITAAQCLIDGMCKVAINWSGG     71 - 140
WHHAKKDEASGFCYLNDAVLGILRLRRKFERILYVDLDLHHGDGVEDAFSFTSKVMTVSLHKFSPGFFPG    141 - 210
TGDVSDVGLGKGRYYSVNVPIQDGIQDEKYYQICESVLKEVYQAFNPKAVVLQLGADTIAGDPMCSFNMT    211 - 280
PVGIGKCLKYILQWQLATLILGGGGYNLANTARCWTYLTGVILGKTLSSEIPDHEFFTAYGPDYVLEITP    281 - 350
SCRPDRNEPHRIQQILNYIKGNLKHVV                                               351 - 377
//

Text Mined References (69)

PMID Year Title
26923266 2016 Regain control of p53: Targeting leukemia stem cells by isoform-specific HDAC inhibition.
26806311 2016 General Base-General Acid Catalysis in Human Histone Deacetylase 8.
26792731 2016 cAMP signaling increases histone deacetylase 8 expression by inhibiting JNK-dependent degradation via autophagy and the proteasome system in H1299 lung cancer cells.
26463496 2015 Biochemical and structural characterization of HDAC8 mutants associated with Cornelia de Lange syndrome spectrum disorders.
26412386 2015 The inhibition of histone deacetylase 8 suppresses proliferation and inhibits apoptosis in gastric adenocarcinoma.
26402585 2015 KDAC8 substrate specificity quantified by a biologically relevant, label-free deacetylation assay.
26387755 2015 HDAC8 Inhibition Specifically Targets Inv(16) Acute Myeloid Leukemic Stem Cells by Restoring p53 Acetylation.
26383163 2015 Histone Deacetylase HDAC8 Promotes Insulin Resistance and ?-Catenin Activation in NAFLD-Associated Hepatocellular Carcinoma.
26200462 2015 HDAC8, A Potential Therapeutic Target for the Treatment of Malignant Peripheral Nerve Sheath Tumors (MPNST).
25836739 2015 Expression of the class 1 histone deacetylases HDAC8 and 3 are associated with improved survival of patients with metastatic melanoma.
25793284 2015 Variable active site loop conformations accommodate the binding of macrocyclic largazole analogues to HDAC8.
25605725 2015 Mechanism of N-Acylthiourea-mediated activation of human histone deacetylase 8 (HDAC8) at molecular and cellular levels.
25516458 2015 Kinetics and thermodynamics of metal-binding to histone deacetylase 8.
25504627 2015 miR-21-3p regulates cardiac hypertrophic response by targeting histone deacetylase-8.
25451941 2015 Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro and in vivo.
25407689 2014 Thermodynamics of binding of structurally similar ligands to histone deacetylase 8 sheds light on challenges in the rational design of potent and isozyme-selective inhibitors of the enzyme.
25321483 2014 HDAC8 and STAT3 repress BMF gene activity in colon cancer cells.
25075551 2014 Compromised structure and function of HDAC8 mutants identified in Cornelia de Lange Syndrome spectrum disorders.
25011684 2014 Histone deacetylase 8 is deregulated in urothelial cancer but not a target for efficient treatment.
24920679 2014 Histone deacetylase 8 regulates cortactin deacetylation and contraction in smooth muscle tissues.
24404147 2014 DEC1 coordinates with HDAC8 to differentially regulate TAp73 and ?Np73 expression.
24403048 2014 Loss-of-function HDAC8 mutations cause a phenotypic spectrum of Cornelia de Lange syndrome-like features, ocular hypertelorism, large fontanelle and X-linked inheritance.
24171457 2013 Loop interactions and dynamics tune the enzymatic activity of the human histone deacetylase 8.
24077923 2013 The up-regulation of histone deacetylase 8 promotes proliferation and inhibits apoptosis in hepatocellular carcinoma.
23482931 2013 SOX4 is a direct target gene of FRA-2 and induces expression of HDAC8 in adult T-cell leukemia/lymphoma.
23430957 2013 Pure curcumin increases the expression of SOCS1 and SOCS3 in myeloproliferative neoplasms through suppressing class I histone deacetylases.
23111066 2013 Histone deacetylases inhibitor sodium butyrate inhibits JAK2/STAT signaling through upregulation of SOCS1 and SOCS3 mediated by HDAC8 inhibition in myeloproliferative neoplasms.
22944197 2013 Changes in histone deacetylase (HDAC) expression patterns and activity of HDAC inhibitors in urothelial cancers.
22889856 2012 X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face.
22885700 2012 HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.
22391568 2013 Histone deacetylase inhibitors suppress mutant p53 transcription via histone deacetylase 8.
22046129 2011 Histone deacetylase 8 is required for centrosome cohesion and influenza A virus entry.
21790156 2011 Structural basis of the antiproliferative activity of largazole, a depsipeptide inhibitor of the histone deacetylases.
21455583 2011 Histone deacetylases 1, 6 and 8 are critical for invasion in breast cancer.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20545365 2010 Structures of metal-substituted human histone deacetylase 8 provide mechanistic inferences on biological function .
20029090 2010 Activation and inhibition of histone deacetylase 8 by monovalent cations.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19355988 2009 Novel structural insights into class I and II histone deacetylases.
19118036 2009 Histone deacetylase 8 in neuroblastoma tumorigenesis.
19070599 2009 Inactivation of CREB mediated gene transcription by HDAC8 bound protein phosphatase.
19053282 2008 Structural studies of human histone deacetylase 8 and its site-specific variants complexed with substrate and inhibitors.
18256683 2008 A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas.
17786334 2007 Expression profile of class I histone deacetylases in human cancer tissues.
17721440 2007 Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex.
16809764 2006 Histone deacetylase 8 safeguards the human ever-shorter telomeres 1B (hEST1B) protein from ubiquitin-mediated degradation.
16681389 2006 Catalytic activity and inhibition of human histone deacetylase 8 is dependent on the identity of the active site metal ion.
16538051 2006 Use of histone deacetylase 8 (HDAC8), a new marker of smooth muscle differentiation, in the classification of mesenchymal tumors of the uterus.
15772651 2005 The DNA sequence of the human X chromosome.
15772115 2005 Histone deacetylase HDAC8 associates with smooth muscle alpha-actin and is essential for smooth muscle cell contractility.
15590418 Screening of histone deacetylases (HDAC) expression in human prostate cancer reveals distinct class I HDAC profiles between epithelial and stromal cells.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15477595 2004 Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor.
15342556 2004 Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.
15242608 2004 Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14701748 2004 Negative regulation of histone deacetylase 8 activity by cyclic AMP-dependent protein kinase A.
14684825 2003 Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays.
12711221 2003 Class II histone deacetylases: versatile regulators.
12509458 2003 The inv(16) fusion protein associates with corepressors via a smooth muscle myosin heavy-chain domain.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11533236 2001 ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain.
10926844 2000 Cloning and characterization of a novel human histone deacetylase, HDAC8.
10922473 2000 Cloning and characterization of human histone deacetylase 8.
10756090 2000 Characterization of a highly complex region in Xq13 and mapping of three isodicentric breakpoints associated with preleukemia.
10748112 2000 Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.
1746601 1991 New X-linked syndrome of mental retardation, gynecomastia, and obesity is linked to DXS255.
1605216 1992 Nomenclature guidelines for X-linked mental retardation.