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AATF (Apoptosis Antagonizing Transcription Factor)

Identity

Other namesDED
CHE1
CHE-1
HGNC (Hugo) AATF
Location 17q12
Location_base_pair Starts at 35306175 and ends at 35414171 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Note AATF affects cell growth by interfering with the recruitment of HDAC1 by retinoblastoma protein. Its over-expression activates DNA synthesis in quiescent NIH-3T3 cells through HFDAC1 displacement. Also, it is considered as a general HDAC1 competitor and its down-regulation is involved in colon carcinoma cell proliferation. It is also found to bind to TSG101 in a process that enhances androgen receptor-mediated transcription by promoting its mono-ubiquitination. It has been observed lately that AATF 12th exon truncation by HIV-1 specific encoded miRNA leads to HIV-1 disease progression. On other side its over-expression has been observed in various leukemic cell lines and is considered to be important for maintaining leukemic state.

DNA/RNA

Note Protein AATF (Apoptosis-antagonizing transcription factor) (Rb-binding protein Che-1). Total gene size being 107.996 kb and having transcribed region of 2.141 kb it codes for 561 amino acids.
Description Spans on 107.996 kb on genomic fragment and contains 12 exons.
Transcription 2023 bp mRNA
Pseudogene No pseudogenes for AATF are known.

Protein

Note 561 amino acids long protein contains POLR2J binding site at 273-315 amino acids, RB1 binding site at 316-372 amino acids, RB1 and SP1 binding site at 373-472 amino acids and Glu-rich region at 96-195 amino acids.
Description AATF was identified as an interacting partner with MAP3K12/DLK which happens to be a protein kinase known to be involved in the induction of cell apoptosis. Its protein contains a leucine zipper, which is a characteristic motif of transcription factors, and was shown to exhibit strong transactivation activity when fused to Gal4 DNA binding domain. Overexpression of this gene interfered with MAP3K12 induced apoptosis.
Expression Ubiquitously expressed. Expressed at high levels in brain, heart, kidney, placenta, thymus and moderate levels in blood mononuclear cells.
Localisation Nucleus; nucleolus.
Function It functions as a general inhibitor of the histone deacetylase HDAC1. Binding to the pocket region of RB1 may displace HDAC1 from RB1/E2F complexes, leading to activation of E2F target genes and cell cycle progression. Conversely, displacement of HDAC1 from SP1 bound to the CDKN1A promoter leads to increased expression of this CDK inhibitor and blocks cell cycle progression. Also antagonizes PAWR mediated induction of aberrant amyloid peptide production in Alzheimer disease (presenile and senile dementia), although the molecular basis for this phenomenon has not been described to date.

Mutations

Note Several polymorphisms have been identified and but none of them has shown any association with any disease.

Implicated in

Entity Leukemia
Note AATF plays a major role in immortalization of leukemic cells through up-regulation of Bcl2 gene expression.
Disease Haematopoitic malignancies
 
AATF dependent cross talk between cellular apoptosis and proliferation.
  
Entity AIDS
Note HIV-1 encodes a specific miRNA that has the inherent capacity to cleave 12th exon of AATF gene resulting in truncated AATF gene product which is destined to undergo degradation. Down-regulation of AATF gene expression is always accompanied by significant reduction in cell viability and down-regulation of gene coding for dicer which plays a crucial role in providing immunity at the nucleic acid level.
Disease Immunodeficiency, Lymphoadenopathy, Kaposi's sarcoma, AIDS dementia
 
HIV-1 encoded miRNA dependent AATF gene down-regulation and subsequent cell death.
  

External links

Nomenclature
HGNC (Hugo)AATF   19235
Entrez_Gene (NCBI)AATF  26574  apoptosis antagonizing transcription factor
Cards
AtlasAATFID534ch17q11
GeneCards (Weizmann)AATF
Ensembl (Hinxton)ENSG00000108270 [Gene_View]  chr17:35306175-35414171 [Contig_View]  AATF [Vega]
AceView (NCBI)AATF
Genatlas (Paris)AATF
euGene (Indiana)26574
SOURCE (Stanford)NM_012138
Genomic and cartography
GoldenPath (UCSC)AATF  -  17q12   chr17:35306175-35414171 +  17q12   [Description]    (hg19-Feb_2009)
EnsemblAATF - 17q12 [CytoView]
Mapping of homologs : NCBIAATF [Mapview]
OMIM608463   
Gene and transcription
Genbank (Entrez)AF083208 AF161395 AJ249940 AK026173 AK057229
RefSeq transcript (SRS)NM_012138
RefSeq transcript (Entrez)NM_012138
RefSeq genomic (SRS)AC_000149 NC_000017 NT_010783 NW_001838433
RefSeq genomic (Entrez)AC_000149 NC_000017 NT_010783 NW_001838433
Consensus coding sequences : CCDS (NCBI)AATF
Cluster EST : UnigeneHs.195740 [ SRS ] Hs.195740 [ NCBI ]
Alternative Splicing : Fast-db (Paris)8852
Alternative Splicing GalleryENSG00000108270
Gene ExpressionAATF [ NCBI-GEO ]   AATF [ EBI - ARRAY_EXPRESS ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9NY61 (SRS) Q9NY61 (Uniprot)
With graphics : InterProQ9NY61
Splice isoforms : SwissVarQ9NY61(Swissvar)
Domains : Interpro (SRS)TRAUB   
Domains : Interpro (EBI)TRAUB   
Related proteins : CluSTrQ9NY61
Domain families : Pfam (SRS)TRAUB (PF08164)   
Domain families : Pfam (Sanger)TRAUB (PF08164)   
Domain families : Pfam (NCBI)pfam08164   
Blocks (Seattle)Q9NY61
Human Protein AtlasENSG00000108270
HPRD12236
IPIIPI00302238   
Protein Interaction databases
DIP (DOE-UCLA)Q9NY61
IntAct (EBI)Q9NY61
FunCoupENSG00000108270
REACTOMEAATF
BioGRIDAATF
InParanoidQ9NY61
Interologous Interaction database Q9NY61
Polymorphism : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)AATF
SNP (GeneSNP Utah)AATF
SNP : HGBaseAATF
Genetic variants : HAPMAPAATF
Somatic Mutations in Cancer : COSMICAATF 
CONAN: Copy Number AnalysisAATF 
Mutations and Diseases : HGMDAATF
OMIM608463   
GENETests608463   
Disease Genetic AssociationAATF
Huge Navigator AATF [HugePedia]  AATF [HugeCancerGEM]
Genomic VariantsAATF
snp3D : Map Gene to Disease
General knowledge
Homologs : HomoloGeneAATF
Homology/Alignments : Family Browser (UCSC)AATF
Phylogenetic Trees/Animal Genes : TreeFamAATF
Chemical/Protein Interactions : CTD26574
Chemical/Pharm GKB GenePA128395780
Clinical trialAATF
Cancer Resource (Charite)ENSG00000108270
Ontology : AmiGOsequence-specific DNA binding transcription factor activity  protein binding  nucleus  nucleolus  cytoplasm  Golgi apparatus  centrosome  focal adhesion  apoptotic process  anti-apoptosis  response to DNA damage stimulus  cell adhesion  regulation of mitotic cell cycle  induction of apoptosis by extracellular signals  protein domain specific binding  negative regulation of superoxide anion generation  embryonic cleavage  ribosome biogenesis  negative regulation of amyloid precursor protein biosynthetic process  leucine zipper domain binding  positive regulation of transcription from RNA polymerase II promoter  nerve growth factor receptor signaling pathway  tau protein binding  negative regulation of reactive oxygen species metabolic process  
Ontology : EGO-EBIsequence-specific DNA binding transcription factor activity  protein binding  nucleus  nucleolus  cytoplasm  Golgi apparatus  centrosome  focal adhesion  apoptotic process  anti-apoptosis  response to DNA damage stimulus  cell adhesion  regulation of mitotic cell cycle  induction of apoptosis by extracellular signals  protein domain specific binding  negative regulation of superoxide anion generation  embryonic cleavage  ribosome biogenesis  negative regulation of amyloid precursor protein biosynthetic process  leucine zipper domain binding  positive regulation of transcription from RNA polymerase II promoter  nerve growth factor receptor signaling pathway  tau protein binding  negative regulation of reactive oxygen species metabolic process  
Other databases
Probes
Probes : ImagenesAATF Related clones (RZPD - Berlin)
Litterature
PubMed39 Pubmed reference(s) in Entrez
PubGeneAATF
iHOPAATF

Bibliography

Che-1 affects cell growth by interfering with the recruitment of HDAC1 by Rb.
Bruno T, De Angelis R, De Nicola F, Barbato C, Di Padova M, Corbi N, Libri V, Benassi B, Mattei E, Chersi A, Soddu S, Floridi A, Passananti C, Fanciulli M
Cancer cell. 2002 ; 2 (5) : 387-399.
PMID 12450794
 
Che-1 arrests human colon carcinoma cell proliferation by displacing HDAC1 from the p21WAF1/CIP1 promoter.
Di Padova M, Bruno T, De Nicola F, Iezzi S, D'Angelo C, Gallo R, Nicosia D, Corbi N, Biroccio A, Floridi A, Passananti C, Fanciulli M
The Journal of biological chemistry. 2003 ; 278 (38) : 36496-36504.
PMID 12847090
 
TSG101 interacts with apoptosis-antagonizing transcription factor and enhances androgen receptor-mediated transcription by promoting its monoubiquitination.
Burgdorf S, Leister P, Scheidtmann KH
The Journal of biological chemistry. 2004 ; 279 (17) : 17524-17534.
PMID 14761944
 
Evidence and Nature of a novel miRNA Encoded by HIV-1.
Kaul D, Khanna A, Suman
Proc Indian Natn Sci Acad. 1972.
 
Functional characterization of AATF transcriptome in human leukemic cells.
Kaul D, Mehrotra A
Molecular and cellular biochemistry. 2007 ; 297 (1-2) : 215-220.
PMID 17006618
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written12-2006Deepak Kaul, Amit Khanna

Citation

This paper should be referenced as such :
Kaul D, Khanna A . AATF (Apoptosis Antagonizing Transcription Factor). Atlas Genet Cytogenet Oncol Haematol. December 2006 .
URL : http://AtlasGeneticsOncology.org/Genes/AATFID534ch17q11.html

This paper is referenced by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/38401/1/12-2006-AATFID534ch17q11.pdf   [ Bibliographic record ]

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indexed on : Sat Apr 28 15:05:34 CEST 2012

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