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Pleiotropic Functions of RB Protein in Tumor Suppression

Naoyuki Hayashi, Chiaki Takahashi

RB tumor suppressor gene product (pRB) has been proposed to interact with more than 200 cellular proteins. In addition to the phosphorylation, carried out by cyclindependent kinases (CDKs), pRB undergoes various types of post-translational modifications. The post-translational modifications of pRB affect the binding status with numerous effector molecules including the E2F family transcription factors, proteins with LxCxE motifs, and proteasome-related proteins. This variability of effector molecules enables pRB to exert pleiotropic functions. These functions also differ remarkably depending on the cell lineage and cellular context. Therefore, many recent reviews have referred to pRB as an adaptor protein based on its functions, in addition to as a pocket protein based on its structure. E2F family members have been critically implicated in pRB functions to drive cell cyclerelated events, yet consists minority of effector molecules in terms of number. In addition, E2Fs also target numerous genes those are not directly involved in the cell cycle control. Therefore, we speculate that pRB performs numerous cell cycle-independent functions in both E2F-dependent and -independent manners. This review, although without strictly discriminating between E2F-dependent and -independent functions, aims to describe the canonical and non-canonical functions of pRB.