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Cell Cycle. 2016 Jul 2;15(13):1724-32. doi: 10.1080/15384101.2016.1182267. Epub 2016 May 10.

SUMOylation of Rb enhances its binding with CDK2 and phosphorylation at early G1 phase.

Meng F1,2, Qian J1,2, Yue H1,2, Li X1,2, Xue K1,2.

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a Department of Ophthalmology , Eye and ENT Hospital of Fudan University , Shanghai , China.
b Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University , Shanghai , China.


Retinoblastoma protein (Rb) is a prototypical tumor suppressor that is vital to the negative regulation of the cell cycle and tumor progression. Hypo-phosphorylated Rb is associated with G0/G1 arrest by suppressing E2F transcription factor activity, whereas Rb hyper-phosphorylation allows E2F release and cell cycle progression from G0/G1 to S phase. However, the factors that regulate cyclin-dependent protein kinase (CDK)-dependent hyper-phosphorylation of Rb during the cell cycle remain obscure. In this study, we show that throughout the cell cycle, Rb is specifically small ubiquitin-like modifier (SUMO)ylated at early G1 phase. SUMOylation of Rb stimulates its phosphorylation level by recruiting a SUMO-interaction motif (SIM)-containing kinase CDK2, leading to Rb hyper-phosphorylation and E2F-1 release. In contrast, a SUMO-deficient Rb mutant results in reduced SUMOylation and phosphorylation, weakened CDK2 binding, and attenuated E2F-1 sequestration. Furthermore, we reveal that Rb SUMOylation is required for cell proliferation. Therefore, our study describes a novel mechanism that regulates Rb phosphorylation during cell cycle progression.


CDK2; Rb; SUMO-interaction motif (SIM); SUMOylation; cell cycle; phosphorylation

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