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PMID:20368352

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Citation

Yuan, Z, Villagra, A, Peng, L, Coppola, D, Glozak, M, Sotomayor, EM, Chen, J, Lane, WS and Seto, E (2010) The ATDC (TRIM29) protein binds p53 and antagonizes p53-mediated functions. Mol. Cell. Biol. 30:3004-15

Abstract

The ataxia telangiectasia group D-complementing (ATDC) gene product, also known as TRIM29, is a member of the tripartite motif (TRIM) protein family. ATDC has been proposed to form homo- or heterodimers and to bind nucleic acids. In cell cultures, ATDC expression leads to rapid growth and resistance to ionizing radiation (IR), whereas silencing of ATDC expression decreases growth rates and increases sensitivity to IR. Although ATDC is overexpressed in many human cancers, the biological significance of ATDC overexpression remains obscure. We report here that ATDC increases cell proliferation via inhibition of p53 nuclear activities. ATDC represses the expression of p53-regulated genes, including p21 and NOXA. Mechanistically, ATDC binds p53, and this interaction is potentially fine-tuned by posttranslational acetylation of lysine 116 on ATDC. The association of p53 and ATDC results in p53 sequestration outside of the nucleus. Together, these results provide novel mechanistic insights into the function of ATDC and offer an explanation for how ATDC promotes cancer cell proliferation.

Links

PubMed PMC2876676 Online version:10.1128/MCB.01023-09

Keywords

Acetylation; Animals; Apoptosis; Cell Proliferation; Cell Transformation, Neoplastic/pathology; Cyclin-Dependent Kinase Inhibitor p21/genetics; DNA-Binding Proteins/metabolism; HCT116 Cells; Humans; Lysine/metabolism; Mice; Phosphoserine/metabolism; Promoter Regions, Genetic/genetics; Protein Binding; Protein Transport; Proteins/genetics; Subcellular Fractions/metabolism; Transcription Factors/metabolism; Transcriptional Activation/genetics; Tumor Suppressor Protein p53/genetics; Tumor Suppressor Protein p53/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:P53

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(MGI:MGI:1930146)

Seeded From UniProt

complete

MOUSE:TRI29

acts_upstream_of_or_within

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98834

P

  • has_input:(MGI:MGI:1930146)

Seeded From UniProt

complete

MOUSE:TRI29

enables

GO:0002039: p53 binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:TRI29

acts_upstream_of_or_within

GO:1900181: negative regulation of protein localization to nucleus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:P53

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

has_regulation_target:(MGI:MGI:1930146)

Seeded From UniProt

complete


See also

References

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