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FLASH GENE
Symbol AATF contributors: mct - updated : 23-09-2015
HGNC name apoptosis antagonizing transcription factor
HGNC id 19235
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Digestiveintestinelarge intestinecolon lowly
Endocrineadrenal gland   moderately
Lymphoid/Immunespleen   moderately
 thymus   highly
Nervousbrain   highly
Reproductivefemale systemuteruscervix highly
Skin/Tegumentskin   moderately
Urinarykidney   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connective   predominantly
Lymphoid    
Muscularstriatumskeletal moderately
cell lineage
cell lines
fluid/secretion moderately in lymph
at STAGE
physiological period pregnancy
Text placenta
PROTEIN
PHYSICAL PROPERTIES acid
STRUCTURE
motifs/domains
  • higly acidic domain
  • a putative leucine zipper
  • HOMOLOGY
    interspecies ortholog to rattus Aatf (84.9 pc)
    ortholog to murine Aatf (84.1 pc)
    Homologene
    FAMILY
  • AATF family
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleolus
    text
  • localizes at interphase centrosomes, where it accumulates following DNA damage or spindle poisons
  • basic FUNCTION
  • involved in the regulation of gene transcription and cell proliferation
  • inhibiting the RB growth-suppressing function by interfering with RB-mediated HDAC1 recruitment on E2F target gene promoters
  • acting as HDAC1 competitor (by displacing HDAC1 from the CDKN1A promoter) and its down-regulation is involved in colon carcinoma cell proliferation
  • contributing to the maintenance of the G2/M checkpoint induced by DNA damage
  • transcriptionally activates AKT1 gene through STAT3, which sustains KT1 activation and promotes cell survival
  • RNA polymerase II binding protein involved in the regulation of gene transcription and, in response to DNA damage, promotes TP53 transcription
  • important role in survival of cells expressing mutant TP53
  • nucleolar stress sensor, which is required as a cofactor for JUN-mediated apoptosis
  • activating XIAP expression in response to DNA damage
  • plays an important role in DNA damage response (DDR) and its contribution seems to be relevant for the spindle assembly checkpoint
  • involved in transcriptional regulation, cell cycle control, DNA damage responses and in the execution of cell death programs
  • RNA polymerase II-binding protein that is involved in the regulation of gene transcription, which undergoes stabilization and accumulation in response to DNA damage
  • important role in the cellular response to DNA damage
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, antiapoptosis
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • hyperphosphorylated during the G1/S phase transition
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • DLK/ZIP kinase, MAP3K12 (induced apoptosis)
  • interacting with TSG101(functioning as cooperative coactivators in androgen receptor-mediated transcription)
  • critical regulator of the cellular outcome of the TP53 response
  • nucleolar stress sensor, which is required as a cofactor for JUN-mediated apoptosis
  • binding to PAWR, POLR2J, RB1/RB, RBL1/P107, RBL2/P130, SP1 and MAPT
  • interacts directly with nuclear hormone receptors to enhance their transactivation
  • HIPK2, a proapoptotic kinase, is involved in AATF degradation (HIPK2 interacts with AATF and, upon genotoxic stress, phosphorylates it at specific residues)
  • TP53/AATF interaction results in preferential transactivation of growth arrest TP53 target genes over its pro-apoptotic target genes
  • cell & other
    REGULATION
    induced by by ER stress through the EIF2AK3 pathway
    Other down-regulated during the apoptotis
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in colon and kidney carcinoma
    tumoral     --over  
    overexpressed ubiquitously in all the leukemic cell lines
    constitutional       loss of function
    mediates a self-perpetuating cycle of cell death
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    attractive, still theoretical, therapeutic target for cancer treatments
    cancer  
    AATF-silencing can be used to induce apoptosis and regulate ER expression in breast cancer cells for therapeutic interventions.
    ANIMAL & CELL MODELS
  • exposure of Aatf(+/-) mice to ionizing radiations resulted in enhanced apoptosis of thymocytes, compared with WT mice