细胞生长
细胞生物学
E2F1
细胞周期蛋白依赖激酶2
调节器
细胞周期
生物
细胞周期蛋白
线粒体
基因沉默
周期素
癌症研究
细胞周期蛋白
细胞凋亡
生物化学
基因
作者
Ye Sang,Jinyu Liu,Fengyi Wang,Xiao-Yu Luo,Zi‐Qi Chen,Shi-Mei Zhuang,Ying Zhu
标识
DOI:10.1016/j.ymthe.2022.04.012
摘要
The roles of micropeptides in cell cycle regulation and cancer development remain largely unknown. Here we found that a micropeptide STMP1 (small transmembrane protein 1) was up-regulated in multiple malignancies including hepatocellular carcinoma (HCC), and its high level was associated with short recurrence-free survival of HCC patients. Gain- and loss-of-function analyses revealed that STMP1 accelerated cell proliferation and clonogenicity in vitro and tumor growth in vivo, and silencing STMP1 blocked G1/S transition. Mechanistically, STMP1 promoted the mRNA and protein levels of CCNE2, CDK2, and E2F1. STMP1 was localized in the inner membrane of mitochondria and interacted with mitochondrial complex IV and then enhanced its activity. Moreover, treatment with the mitochondrial complex IV inhibitor tetrathiomolybdate dramatically abrogated the promoting effect of STMP1 on cell proliferation and the expression of cyclin E2, CDK2, and E2F1. These results suggest that STMP1 may promote G1/S transition and cell proliferation by enhancing mitochondrial complex IV activity, which highlights STMP1 as a new regulator of the cell cycle and a potential target for anti-cancer therapy.
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