Ba Qian, Li Xiaoguang, Huang Chao, Li Junyang, Fu Yijing, Chen Peizhan, Duan Juan, Hao Miao, Zhang Yinghua, Li Jingquan, Sun Chuanqi, Ying Hao, Song Haiyun, Zhang Ruiwen, Shen Zhiyuan, Wang Hui
School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
J Mol Cell Biol. 2017 Jun 1;9(3):209-219. doi: 10.1093/jmcb/mjx019.
Extraribosomal functions of ribosomal proteins (RPs) have gained much attention for their implications in tumorigenesis and progression. However, the regulations for transition between the ribosomal and extraribosomal functions of RPs are rarely reported. Herein, we identified a ribosomal protein S7-interacting partner, BCCIPβ, which modulates the functional conversion of S7. Through the N-terminal acidic domain, BCCIPβ interacts with the central basic region in S7 and regulates the extraribosomal distribution of S7. BCCIPβ deficiency abrogates the ribosomal accumulation but enhances the ribosome-free location of S7. This translocation further impairs protein synthesis and triggers ribosomal stress. Consequently, BCCIPβ deficiency suppresses the ribosomal function and initiates the extraribosomal function of S7, resulting in restriction of cell proliferation. Moreover, clinically relevant S7 mutations were found to dampen the interaction with BCCIPβ and facilitate the functional transition of S7. In conclusion, BCCIPβ, as a S7 modulator, contributes to the regulation of ribosomal and extraribosomal functions of S7 and has implications in cell growth and tumor development.
核糖体蛋白（RPs）的核糖体外功能因其在肿瘤发生和进展中的作用而备受关注。然而，关于RPs核糖体功能和核糖体外功能之间转换的调控却鲜有报道。在此，我们鉴定出一种与核糖体蛋白S7相互作用的蛋白BCCIPβ，它可调节S7的功能转换。通过其N端酸性结构域，BCCIPβ与S7的中央碱性区域相互作用，并调节S7在核糖体外的分布。缺乏BCCIPβ会消除S7在核糖体上的积累，但会增加其游离于核糖体的位置。这种易位进一步损害蛋白质合成并引发核糖体应激。因此，缺乏BCCIPβ会抑制核糖体功能并启动S7的核糖体外功能，从而导致细胞增殖受限。此外，还发现临床相关的S7突变会减弱其与BCCIPβ的相互作用，并促进S7的功能转变。总之，BCCIPβ作为S7的调节剂，有助于调控S7的核糖体功能和核糖体外功能，并对细胞生长和肿瘤发展具有重要意义。
