The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity.
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 functions, 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 germline levels of some RPs in human cancers as well as in patients of Diamond-Blackfan anemia 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.
Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang, 310029, China.
Xilong
X
Xu
Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang, 310029, China. xiufang@zju.edu.cn.
Xiufang
X
Xiong
Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang, 310029, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, Zhejiang University, Zhejiang, 310029, China.|Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 48109, USA.
Yi
Y
Sun
D063646:Carcinogenesis; D049109:Cell Proliferation / Q000502:physiology*; D016678:Genome; D006801:Humans; D012269:Ribosomal Proteins / Q000502:physiology*
D012269:Ribosomal Proteins
MDM2; genomic integrity; p53; ribosomal protein; ribosomal stress; tumorigenesis