AATF (Apoptosis Antagonizing Transcription Factor)

2006-12-01   Deepak Kaul , Amit Khanna 

Department of Expt. Medicine &Biotechnology, Postgraduate Institute of Medical Education &Research, Chandigarh- 160 012, India

Identity

HGNC
LOCATION
17q12
LOCUSID
ALIAS
BFR2,CHE-1,CHE1,DED
FUSION GENES

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.

Proteins

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 name
Leukemia
Note
AATF plays a major role in immortalization of leukemic cells through up-regulation of Bcl2 gene expression.
Disease
Haematopoitic malignancies
Atlas Image
AATF dependent cross talk between cellular apoptosis and proliferation.
Entity name
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, Kaposis sarcoma, AIDS dementia
Atlas Image
HIV-1 encoded miRNA dependent AATF gene down-regulation and subsequent cell death.

Bibliography

Pubmed IDLast YearTitleAuthors
124507942002Che-1 affects cell growth by interfering with the recruitment of HDAC1 by Rb.Bruno T et al
147619442004TSG101 interacts with apoptosis-antagonizing transcription factor and enhances androgen receptor-mediated transcription by promoting its monoubiquitination.Burgdorf S et al
128470902003Che-1 arrests human colon carcinoma cell proliferation by displacing HDAC1 from the p21WAF1/CIP1 promoter.Di Padova M et al
170066182007Functional characterization of AATF transcriptome in human leukemic cells.Kaul D et al

Other Information

Locus ID:

NCBI: 26574
MIM: 608463
HGNC: 19235
Ensembl: ENSG00000275700

Variants:

dbSNP: 26574
ClinVar: 26574
TCGA: ENSG00000275700
COSMIC: AATF

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000275700ENST00000610798A0A087WWS8
ENSG00000275700ENST00000613840A0A087WW41
ENSG00000275700ENST00000616434A0A087WTH8
ENSG00000275700ENST00000619387Q9NY61

Expression (GTEx)

0
10
20
30
40
50
60
70
80
90

Pathways

PathwaySourceExternal ID
Signal TransductionREACTOMER-HSA-162582
Signalling by NGFREACTOMER-HSA-166520
p75 NTR receptor-mediated signallingREACTOMER-HSA-193704
Cell death signalling via NRAGE, NRIF and NADEREACTOMER-HSA-204998
NRAGE signals death through JNKREACTOMER-HSA-193648

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
205322022010Use of genome-wide expression data to mine the "Gray Zone" of GWA studies leads to novel candidate obesity genes.34
198345352009Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging.27
257705842015Che-1-induced inhibition of mTOR pathway enables stress-induced autophagy.27
124507942002Che-1 affects cell growth by interfering with the recruitment of HDAC1 by Rb.26
229098212012AATF/Che-1 acts as a phosphorylation-dependent molecular modulator to repress p53-driven apoptosis.26
147619442004TSG101 interacts with apoptosis-antagonizing transcription factor and enhances androgen receptor-mediated transcription by promoting its monoubiquitination.23
174681072007The prolyl isomerase Pin1 affects Che-1 stability in response to apoptotic DNA damage.23
174887772007NRAGE associates with the anti-apoptotic factor Che-1 and regulates its degradation to induce cell death.23
207081542010Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation.19
259962912015Che-1 modulates the decision between cell cycle arrest and apoptosis by its binding to p53.18

Citation

Deepak Kaul ; Amit Khanna

AATF (Apoptosis Antagonizing Transcription Factor)

Atlas Genet Cytogenet Oncol Haematol. 2006-12-01

Online version: http://atlasgeneticsoncology.org/gene/534/aatf