Although ribosomal proteins are known for playing an essential role in ribosome assembly and protein translation,their ribosomeindependent functions have also been greatly appreciated.Over the past decade,more than a ...Although ribosomal proteins are known for playing an essential role in ribosome assembly and protein translation,their ribosomeindependent functions have also been greatly appreciated.Over the past decade,more than a dozen of ribosomal proteins have been found to activate the tumor suppressor p53 pathway in response to ribosomal stress.In addition,these ribosomal proteins are involved in various physiological and pathological processes.This review is composed to overview the current understanding of how ribosomal stress provokes the accumulation of ribosome-free ribosomal proteins,as well as the ribosome-independent functions of ribosomal proteins in tumorigenesis,immune signaling,and development.Wealso propose the potential of applying these pieces of knowledge to the development of ribosomal stress-based cancer therapeutics.展开更多
Ribosomal proteins （RPs）, the essential components of the ribosome, are a family of RNA-binding proteins, which play prime roles in ribosome biogenesis and protein translation. Recent studies revealed that RPs have ...Ribosomal proteins （RPs）, the essential components of the ribosome, are a family of RNA-binding proteins, which play prime roles in ribosome biogenesis and protein translation. Recent studies revealed that RPs have additional extra-ribosomal func- tions, independent of protein biosynthesis, in regulation of diverse cellular processes. Here, we review recent advances in our understanding of how RPs regulate apoptosis, cell cycle arrest, cell proliferation, neoplastic transformation, cell migration and invasion, and tumorigenesis through both MDM2/p53-dependent and p53-independent mechanisms. We also discuss the roles of RPs in the maintenance of genome integrity via modulating DNA damage response and repair. We further discuss mutations or deletions at the somatic or gennline levels of some RPs in human cancers as well as in patients of Diamond-Blackfan ane- mia and 5q- syndrome with high susceptibility to cancer development. Moreover, we discuss the potential clinical application, based upon abnormal levels of RPs, in biomarker development for early diagnosis and/or prognosis of certain human cancers. Finally, we discuss the pressing issues in the field as future perspectives for better understanding the roles of RPs in human cancers to eventually benefit human health.展开更多
Extraribosomal functions of ribosomal proteins （RPs） have gained much attention for their implications in tumorigenesis and pro- gression. However, the regulations for transition between the ribosomal and extraribos...Extraribosomal functions of ribosomal proteins （RPs） have gained much attention for their implications in tumorigenesis and pro- gression. 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 dis- tribution of S7. BCCIPI~ 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 conclu- sion, BCCIPβ, as a S7 modulator, contributes to the regulation of ribosomal and extraribosomai functions of S7 and has implica- tions in cell growth and tumor development.展开更多
基金H.L.was supported by NIH-NCI grants CA095441 and CA172468the Reynolds and Ryan Families chair fund.
文摘Although ribosomal proteins are known for playing an essential role in ribosome assembly and protein translation,their ribosomeindependent functions have also been greatly appreciated.Over the past decade,more than a dozen of ribosomal proteins have been found to activate the tumor suppressor p53 pathway in response to ribosomal stress.In addition,these ribosomal proteins are involved in various physiological and pathological processes.This review is composed to overview the current understanding of how ribosomal stress provokes the accumulation of ribosome-free ribosomal proteins,as well as the ribosome-independent functions of ribosomal proteins in tumorigenesis,immune signaling,and development.Wealso propose the potential of applying these pieces of knowledge to the development of ribosomal stress-based cancer therapeutics.
基金supported by the National Natural Science Foundation of China (81572708, 31501129 to Xiufang Xiong 81572718 to Yi Sun)
文摘Ribosomal proteins （RPs）, the essential components of the ribosome, are a family of RNA-binding proteins, which play prime roles in ribosome biogenesis and protein translation. Recent studies revealed that RPs have additional extra-ribosomal func- tions, independent of protein biosynthesis, in regulation of diverse cellular processes. Here, we review recent advances in our understanding of how RPs regulate apoptosis, cell cycle arrest, cell proliferation, neoplastic transformation, cell migration and invasion, and tumorigenesis through both MDM2/p53-dependent and p53-independent mechanisms. We also discuss the roles of RPs in the maintenance of genome integrity via modulating DNA damage response and repair. We further discuss mutations or deletions at the somatic or gennline levels of some RPs in human cancers as well as in patients of Diamond-Blackfan ane- mia and 5q- syndrome with high susceptibility to cancer development. Moreover, we discuss the potential clinical application, based upon abnormal levels of RPs, in biomarker development for early diagnosis and/or prognosis of certain human cancers. Finally, we discuss the pressing issues in the field as future perspectives for better understanding the roles of RPs in human cancers to eventually benefit human health.
文摘Extraribosomal functions of ribosomal proteins （RPs） have gained much attention for their implications in tumorigenesis and pro- gression. 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 dis- tribution of S7. BCCIPI~ 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 conclu- sion, BCCIPβ, as a S7 modulator, contributes to the regulation of ribosomal and extraribosomai functions of S7 and has implica- tions in cell growth and tumor development.
