The ATDC (TRIM29) protein binds p53 and antagonizes p53-mediated functions.
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.
Yuan
Zhigang
Z
H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
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
D000107:Acetylation; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D008239:Lysine / Q000378:metabolism; D051379:Mice; D010768:Phosphoserine / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D021381:Protein Transport; D011506:Proteins / Q000235:genetics; D013347:Subcellular Fractions / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; C472286:Noxa1 protein, mouse; D011506:Proteins; C087296:TRIM29 protein, human; C550082:TRIM29 protein, mouse; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D010768:Phosphoserine; D008239:Lysine