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FLASH GENE
Symbol AATF contributors: mct - updated : 23-09-2015
HGNC name apoptosis antagonizing transcription factor
HGNC id 19235
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
12 - 2172 63 560 - -
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