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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
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Nervousnerve   highly
 spinal cord   highly
Respiratoryrespiratory tractlarynx  highly
Urinarykidney   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal highly
Nervouscentral   
cell lineage
cell lines
fluid/secretion
at STAGE
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