H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
Mol Cell Biol. 2010 Jun;30(12):3004-15. doi: 10.1128/MCB.01023-09. Epub 2010 Apr 5.
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.
共济失调毛细血管扩张症突变基因 D 互补（ATDC）产物，也称为 TRIM29，是三肽重复结构（TRIM）蛋白家族的一员。ATDC 被提议形成同二聚体或异二聚体，并与核酸结合。在细胞培养中，ATDC 的表达导致快速生长和对电离辐射（IR）的抗性，而 ATDC 表达的沉默降低了生长速率并增加了对 IR 的敏感性。尽管 ATDC 在许多人类癌症中过度表达，但 ATDC 过度表达的生物学意义仍然不清楚。我们在这里报告 ATDC 通过抑制 p53 核活性来增加细胞增殖。ATDC 抑制 p53 调节基因的表达，包括 p21 和 NOXA。在机制上，ATDC 结合 p53，这种相互作用可能通过 ATDC 赖氨酸 116 的翻译后乙酰化进行微调。p53 和 ATDC 的结合导致 p53 被隔离在核外。总之，这些结果为 ATDC 的功能提供了新的机制见解，并解释了 ATDC 如何促进癌细胞增殖。
