DNAJB9 抑制 p53 依赖性癌基因诱导的衰老并诱导细胞转化。

DNAJB9 Inhibits p53-Dependent Oncogene-Induced Senescence and Induces Cell Transformation.

机构信息

Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine, Chuncheon 24341, Korea.

Department of Biological Sciences, Kangwon National University, Chuncheon 24341, Korea.

出版信息

Mol Cells. 2020 Apr 30;43(4):397-407. doi: 10.14348/molcells.2020.2231.

DOI:10.14348/molcells.2020.2231

PMID:32264658

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7191047/

Abstract

is known to be a member of the molecular chaperone gene family, whose cellular function has not yet been fully characterized. Here, we investigated the cellular function of DNAJB9 under strong mitogenic signals. We found that DNAJB9 inhibits p53-dependent oncogene-induced senescence (OIS) and induces neoplastic transformation under oncogenic RAS activation in mouse primary fibroblasts. In addition, we observed that DNAJB9 interacts physically with p53 under oncogenic RAS activation and that the p53-interacting region of DNAJB9 is critical for the inhibition of p53-dependent OIS and induction of neoplastic transformation by DNAJB9. These results suggest that DNAJB9 induces cell transformation under strong mitogenic signals, which is attributable to the inhibition of p53-dependent OIS by physical interactions with p53. This study might contribute to our understanding of the cellular function of DNAJB9 and the molecular basis of cell transformation.

摘要

DNAJB9 是分子伴侣基因家族的成员，但其细胞功能尚未完全阐明。在这里，我们研究了 DNAJB9 在强烈有丝分裂信号下的细胞功能。我们发现 DNAJB9 抑制 p53 依赖性癌基因诱导的衰老（OIS），并在原代小鼠成纤维细胞中激活致癌 RAS 时诱导肿瘤转化。此外，我们观察到在致癌 RAS 激活下，DNAJB9 与 p53 发生物理相互作用，并且 DNAJB9 与 p53 相互作用的区域对于抑制 p53 依赖性 OIS 和由 DNAJB9 诱导的肿瘤转化是至关重要的。这些结果表明，DNAJB9 在强烈有丝分裂信号下诱导细胞转化，这归因于与 p53 的物理相互作用抑制 p53 依赖性 OIS。这项研究可能有助于我们理解 DNAJB9 的细胞功能和细胞转化的分子基础。