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FLASH GENE
Symbol CASP8AP2 contributors: mct/pgu - updated : 22-01-2016
HGNC name caspase 8 associated protein 2
HGNC id 1510
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a NF-kappa B activation domain (NAD)
  • a motif structurally related to CED4/Apaf1
  • two tandem-repeated DED homologous domains
  • a FLASH functional domain
  • HOMOLOGY
    interspecies homolog to murine Casp8ap2
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,nucleus,nucleoplasm,nuclear bodies,PML
    text
  • mainly localized in Cajal bodies
  • localizes to Cajal bodies and promyelocytic leukemia (PML) bodies
  • INPP5D nuclear puncta partially colocalize with CASP8AP2, a component of nuclear bodies
  • basic FUNCTION
  • coordinates downstream NF-kappaB activity via a TRAF2-dependent pathway in the TNF-alpha signaling
  • playing a regulatory role in Fas-mediated apoptosis by activation of caspase 8
  • important component of the machinery required for histone precursor mRNA expression and cell-cycle progression
  • may be a component of the death-inducing signaling complex that includes Fas receptor, Fas-binding adapter FADD, and caspase 8, and plays a regulatory role in Fas-mediated apoptosis
  • playing an essential role for the structure of Cajal bodies
  • regulates both histone gene transcription and mRNA maturation
  • is an essential, non-redundant regulator of histone transcription and cell cycle during embryogenesis
  • under some circumstances, suppresses apoptosis
  • critical for the formation of death complex and the relay of death signal into the cells
  • multifunctional protein involved in multiple cellular processes, reaching from death receptor signaling to regulation of histone gene transcription and histone mRNA processing
  • CELLULAR PROCESS cell cycle, progression
    cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    text induction of apoptosis by extracellular signals
    PATHWAY
    metabolism
    signaling signal transduction
    component of the apoptosis signaling pathway
    a component
  • component of the death-inducing signaling complex in receptor-mediated apoptosis
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to the death effector domain of caspase-8 and to FADD
  • associating with nuclear protein, ataxia-telangiectasia, a component of the cell-cycle-dependent histone gene transcription machinery
  • interacting with histone gene promoter sequences
  • MYB-interacting protein (interacts with the DNA-binding domain of MYB and enhances MYB-dependent reporter activity and expression of endogenous MYB target genes)
  • MYB cooperates with CASP8AP2 in foci associated with active POLR2A, leading to enhancement of MYB-dependent gene activation
  • links the CD95 signaling pathway to the cell nucleus and nuclear bodies
  • interaction between CASP8AP2 and SRRT are required for S phase progression(CASP8AP2 functions in S phase progression through interaction with SRRT)
  • interacting with CPSF3 (catalyses the 3prime-end cleavage of histone pre-mRNAs, requiring the interaction of two U7 snRNP-associated proteins, CASP8AP2 and LSM11)
  • PIAS1 is a common partner for two cancer-related nuclear factors, MYB and CASP8AP2 (functional cooperation between CASP8AP2 and PIAS1 in the enhancement of MYB activity in active nuclear foci)
  • TP73 binds to CASP8AP2 and is part of the complex that regulates histone gene transcription
  • SUMO targets CASP8AP2 for proteasome-dependent degradation, which is associated with recruitment of CASP8AP2 to PML bodies
  • cell & other
    REGULATION
    Other transcriptional activity regulated by sumoylation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in gastric carcinoma tissues
    tumoral     --low  
    low expression of CTBP2 and CASP8AP2 correlated with poor outcome and predicted risk of relapse in pediatric BCP-ALL (B cell precursor acute lymphoblastic leukemia)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • is a promising prognostic indicator in pediatric acute lymphoblastic leukemia (PMID;
  • methylation within the CASP8AP2 promoter correlates with the development of drug resistance and might serve as a biomarker for drug resistance in cancer cells (
  • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    methylation within the CASP8AP2 promoter correlates with the development of drug resistance and might serve as a treatment target for drug resistance in cancer cells
    ANIMAL & CELL MODELS