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FLASH GENE
Symbol HDAC8 contributors: mct/npt - updated : 08-11-2015
HGNC name histone deacetylase 8
HGNC id 13315
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • nine conserved HDAC bloks important for catalytic function
  • a shorter C terminal extension relative to other members of HDAC class I
  • HOMOLOGY
    interspecies homolog to yeast RpD3
    Homologene
    FAMILY
  • histone deacetylase family
  • type 1 subfamily
  • CATEGORY enzyme , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,chromatin/chromosome
    text
  • localized within the nucleus, but is also found in the cytosol of smooth muscle cells where it associates with the alpha-actin cytoskeleton
  • basic FUNCTION
  • regulator of cell proliferation, putative role in cancer development
  • associates with the smooth muscle actin cytoskeleton and may regulate the contractile capacity of smooth muscle cells
  • has inhibitory effect on forskolin-induced CREB activation
  • specifically represses the aberrant expression of homeobox transcription factors such as OTX2 and L1
  • may be activated by either or both of metals (Fe(2+) or Zn(2+))depending on cellular concentrations
  • required for centrosome cohesion and influenza A virus entry
  • play a major role in epigenetic gene silencing during development
  • NIPBL, SMC1A, SMC3, RAD21, and HDAC8 genes codify for the "cohesin complex" playing a role in chromatid adhesion, DNA repair and gene expression regulation
  • CELLULAR PROCESS cell life, proliferation/growth
    nucleotide, chromatin organization, remodeling
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    text transcriptional corepressor
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, other,
  • could bind either or both Fe(2+) or Zn(2+)
  • likely potassium is the predominant monovalent cations bound to HDAC8
  • protein
  • bound to both CREB1 and PPA1 (recombinant HDAC8 results in decreased CREB1 activation and CREB1 mediated gene transcription in response to forskolin application)
  • regulatory mechanism of mutant TP53 transcription via HDAC8
  • SOX4 is a direct target gene of FOSL2 and induces expression of HDAC8 in adult T-cell leukemia/lymphoma
  • cell & other
    REGULATION
    induced by ILK2
    inhibited by trichostatin and histone deacetylase inhibitors
    ASSOCIATED DISORDERS
    corresponding disease(s) CDLS5 , WTSL1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in cancer tissues
    constitutional     --low  
    caused centrosome splitting, which could also be induced by depleting a centriole-linker protein, rootletin
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    HDAC8 inhibitors may have therapeutic potential for the treatment of myeloproliferative neoplasms (MPNs)
    cancer  
    HDAC8-targeting agents might be explored as an adjuvant for tumors carrying a mutant TP53
    ANIMAL & CELL MODELS
  • deletion of Hdac8 in mice leads to perinatal lethality due to skull instability