SENP1-modulated sumoylation regulates retinoblastoma protein (RB) and Lamin A/C interaction and stabilization.
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.
National Cancer Institute, National Institutes of Health, NCI-Frederick, Frederick, MD, USA.
P
P
Sharma
National Cancer Institute, National Institutes of Health, NCI-Frederick, Frederick, MD, USA.
M R
MR
Kuehn
D000818:Animals; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D050684:E2F Transcription Factors / Q000502:physiology; D010450:Endopeptidases / Q000502:physiology*; D034904:Lamin Type A / Q000502:physiology*; D051379:Mice; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D055550:Protein Stability; D016160:Retinoblastoma Protein / Q000502:physiology*; D058207:Sumoylation
D050684:E2F Transcription Factors; D034904:Lamin Type A; D016160:Retinoblastoma Protein; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C501974:Senp1 protein, mouse; D046988:Proteasome Endopeptidase Complex