Center for Experimental Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China; Jiangxi Key Laboratory of Molecular Diagnostics and Precision Medicine, Nanchang, Jiangxi, China.
Center for Experimental Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China; Jiangxi Key Laboratory of Molecular Diagnostics and Precision Medicine, Nanchang, Jiangxi, China.
Biochim Biophys Acta Mol Cell Res. 2021 May;1868(6):118994. doi: 10.1016/j.bbamcr.2021.118994. Epub 2021 Mar 2.
DNAJC5 (DnaJ heat shock protein family (Hsp40) member C5), also known as cysteine tandem protein (CSPα), is important for maintaining the normal function of nerve tissues, but its oncogenic function remains unknown. Here, we report a unique mechanism underlying the oncogenic function of DNAJC5. DNAJC5 protein expression is highly detectable in human hepatocellular carcinoma (HCC) tissues and is strongly related to a poor prognosis among HCC patients. DNAJC5 overexpression promotes HCC cell proliferation and reduced the ratio of cells in G phase of the cell cycle. Furthermore, DNAJC5 interacts with SKP2 and enhances the degradation of p27 (a cyclin-dependent kinase inhibitor1B) by promoting formation of the SKP2-p27 complex. In contrast, DNAJC5 knockdown rescues the SKP2-mediated decrease in p27 protein levels. These results reveal that the DNAJC5-SKP2-p27 pathway is a novel mechanism for the oncogenic function of DNAJC5 in HCC.
DNAJC5（DnaJ 热休克蛋白家族（Hsp40）成员 C5），也称为半胱氨酸串联蛋白（CSPα），对于维持神经组织的正常功能很重要，但它的致癌功能尚不清楚。在这里，我们报告了 DNAJC5 致癌功能的一个独特机制。DNAJC5 蛋白表达在人肝细胞癌（HCC）组织中高度可检测，并且与 HCC 患者的预后不良密切相关。DNAJC5 过表达促进 HCC 细胞增殖，并降低细胞周期 G 期的细胞比例。此外，DNAJC5 与 SKP2 相互作用，并通过促进 SKP2-p27 复合物的形成来增强 p27（一种细胞周期蛋白依赖性激酶抑制剂 1B）的降解。相比之下，DNAJC5 敲低可挽救 SKP2 介导的 p27 蛋白水平下降。这些结果表明，DNAJC5-SKP2-p27 途径是 DNAJC5 在 HCC 中致癌功能的一种新机制。
