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SENP1-modulated sumoylation regulates retinoblastoma protein (RB) and Lamin A/C interaction and stabilization

Oncogene volume 35, pages 6429–6438 (2016)Cite this article

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Abstract

The retinoblastoma tumor suppressor protein (RB) plays a critical role in cell proliferation and differentiation and its inactivation is a frequent underlying factor in tumorigenesis. While the regulation of RB function by phosphorylation is well studied, proteasome-mediated RB protein degradation is emerging as an important regulatory mechanism. Although our understanding of RB turnover is currently limited, there is evidence that the nuclear lamina filament protein Lamin A/C protects RB from proteasomal degradation. Here we show that SUMO1 conjugation of RB and Lamin A/C is modulated by the SUMO protease SENP1 and that sumoylation of both proteins is required for their interaction. Importantly, this SUMO1-dependent complex protects both RB and Lamin A/C from proteasomal turnover.

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Acknowledgements

We thank Stefano Campaner (IIT, Milan) for discussions, and Alessandra Mazzoni (AIRC, Milan), Shyam Sharan (NCI, Frederick), Sushil Rane (NIDDK, Bethesda) and Tom Misteli (NCI, Bethesda) for comments on the manuscript. This work was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health.

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  1. P Sharma

    Present address: 2Current address: National Human Genome Research Institute, Undiagnosed Diseases Program, UDP Translational Laboratory, Rockville, MD, USA.,

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  1. National Cancer Institute, National Institutes of Health, NCI-Frederick, , Frederick, MD, USA

    P Sharma & M R Kuehn

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Correspondence to M R Kuehn.

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Sharma, P., Kuehn, M. SENP1-modulated sumoylation regulates retinoblastoma protein (RB) and Lamin A/C interaction and stabilization. Oncogene 35, 6429–6438 (2016). https://doi.org/10.1038/onc.2016.177

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