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The ATDC (TRIM29) protein binds p53 and antagonizes p53-mediated functions.


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.

SUBMITTER: Yuan Z 

PROVIDER: S-EPMC2876676 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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The ATDC (TRIM29) protein binds p53 and antagonizes p53-mediated functions.

Yuan Zhigang Z   Villagra Alejandro A   Peng Lirong L   Coppola Domenico D   Glozak Michele M   Sotomayor Eduardo M EM   Chen Jiandong J   Lane William S WS   Seto Edward E  

Molecular and cellular biology 20100405 12


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 significa  ...[more]

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