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AATF (Apoptosis Antagonizing Transcription Factor)

Identity

Other namesDED
CHE1
CHE-1
Hugo AATF
Location 17q12
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
HugoAATF
GDBAATF
Entrez_GeneAATF  26574  apoptosis antagonizing transcription factor
Cards
AtlasAATFID534ch17q11
GeneCardsAATF
EnsemblAATF [Search_View]   ENSG00000108270 [Gene_View]
GenatlasAATF
GeneLynxAATF
eGenomeAATF
euGene26574
Genomic and cartography
GoldenPathAATF  -  17q12   chr17:32380288-32488283 +  17q11.2-q12   [Description]    (hg18-Mar_2006)
EnsemblAATF - 17q11.2-q12 [CytoView]
NCBIMapview
OMIMDisease map [OMIM]
HomoloGeneAATF
Gene and transcription
GenbankAF083208 [ ENTREZ ]
GenbankAF161395 [ ENTREZ ]
GenbankAJ249940 [ ENTREZ ]
GenbankAK026173 [ ENTREZ ]
GenbankAK057229 [ ENTREZ ]
RefSeqNM_012138 [ SRS ]    NM_012138 [ ENTREZ ]
RefSeqAC_000060 [ SRS ]    AC_000060 [ ENTREZ ]
RefSeqNC_000017 [ SRS ]    NC_000017 [ ENTREZ ]
RefSeqNT_078100 [ SRS ]    NT_078100 [ ENTREZ ]
RefSeqNW_926817 [ SRS ]    NW_926817 [ ENTREZ ]
AceViewAATF AceView - NCBI
UnigeneHs.195740 [ SRS ]    Hs.195740 [ NCBI ]     HS195740 [ spliceNest ]
Fast-db8852 (alternative variants)
Protein : pattern, domain, 3D structure
SwissProtQ9NY61 [ SRS]    Q9NY61 [ EXPASY ]     Q9NY61 [ INTERPRO ]
InterproIPR012617 TRAUB [ SRS ]    IPR012617 TRAUB [ EBI ]
CluSTrQ9NY61
PfamPF08164 TRAUB [ SRS ]    PF08164 TRAUB [ Sanger ]    pfam08164 [ NCBI-CDD ]
BlocksQ9NY61
HPRD12236
Protein Interaction databases
DIPQ9NY61
IntActQ9NY61
Polymorphism : SNP, mutations, diseases
OMIM608463    [ map ]   
GENECLINICS608463
SNPAATF [dbSNP-NCBI]  
SNPNM_012138 [SNP-NCI]  
SNPAATF [GeneSNPs - Utah]  AATF] [HGBASE - SRS]
HAPMAPAATF [HAPMAP]  
HGMDAATF
General knowledge
Family BrowserAATF [UCSC Family Browser]
SOURCENM_012138
SMDHs.195740
SAGEHs.195740
GOtranscription factor activity [Amigo]  transcription factor activity
GOprotein binding [Amigo]  protein binding
GOnucleus [Amigo]  nucleus
GOanti-apoptosis [Amigo]  anti-apoptosis
PubGeneAATF
TreeFamAATF
CTD26574 [Comparative ToxicoGenomics Database]
Other databases
Probes
ProbeAATF Related clones (RZPD - Berlin)
PubMed
PubMed23 Pubmed reference(s) in LocusLink

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

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Jul 2 08:21:25 2008


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