PTBP1在癌症中促进细胞周期蛋白B1的内部核糖体进入位点介导的翻译。

PTBP1 promotes IRES-mediated translation of cyclin B1 in cancer.

作者信息

Fan Xinyi, Zhao Zitong, Ma Liying, Huang Xuanlin, Zhan Qimin, Song Yongmei

机构信息

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021 China.

Department of Radiation Oncology, Weill Cornell Medical College, New York, NY 10065, USA.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2022 May 25;54(5):696-707. doi: 10.3724/abbs.2022046.

DOI:10.3724/abbs.2022046

PMID:35643957

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9828304/

Abstract

Cyclin B1 is an essential cyclin-dependent protein that involves in the G2/M transition. Multiple studies report that cyclin B1 is upregulated in cancers and promotes cancer progression. However, the mechanism of cyclin B1 upregulation remains unclear. Here we report that the 5'UTR of cyclin B1 mRNA contains an internal ribosome entry site (IRES) by using a bicistronic fluorescent reporter. We show that IRES can initiate the translation of cyclin B1, and the IRES-mediated translation is further activated under cell stress. Interacting trans-acting factors (ITAFs) are required by most IRES to initiate the translation. We find that PTBP1 promotes the IRES-mediated translation of cyclin B1 by binding to the 5'UTR of cyclin B1. On top of that, PTBP1 promotes the malignancy of ESCC cells. Our data suggest that the IRES-mediated translation of cyclin B1 plays an essential role in the cyclin B1 upregulation in cancers.

摘要

细胞周期蛋白B1是一种重要的细胞周期蛋白依赖性蛋白，参与G2/M期转换。多项研究报道，细胞周期蛋白B1在癌症中上调并促进癌症进展。然而，细胞周期蛋白B1上调的机制仍不清楚。在此我们报道，通过使用双顺反子荧光报告基因，细胞周期蛋白B1 mRNA的5'UTR包含一个内部核糖体进入位点（IRES）。我们表明IRES可以启动细胞周期蛋白B1的翻译，并且IRES介导的翻译在细胞应激下进一步被激活。大多数IRES启动翻译需要相互作用的反式作用因子（ITAFs）。我们发现PTBP1通过与细胞周期蛋白B1的5'UTR结合来促进细胞周期蛋白B1的IRES介导的翻译。除此之外，PTBP1促进食管鳞状细胞癌（ESCC）细胞的恶性程度。我们的数据表明，细胞周期蛋白B1的IRES介导的翻译在癌症中细胞周期蛋白B1上调中起重要作用。