SUMO-1 overexpression increases RbAp46 protein stability and suppresses cell growth.

The retinoblastoma suppressor (Rb)-associated protein 46 (RbAp46) is a nuclear protein of 46 kDa and contains four repeats that end with Trp-Asp (WD) residues. In this study, we reveal that the RbAp46 protein level upon SUMO-1 expression was increased. The increasing level of RbAp46 protein by SUMO-1 was not regulated ...
at the transcriptional level. SUMO-1 does not affect the degradation of RbAp46. Co-localization of RbAp46 and SUMO-1 in the nuclei of stable NIH/3T3 cells harboring the inducible Ha-ras(Val12) oncogene (pSVlacOras) designated as 7-4, and protein-protein interaction between RbAp46 and SUMO-1 was also detected by co-immunoprecipitation in these cells. However, SUMO-l-related sumoylation was not involved in the modification of RbAp46. It is possibly that SUMO-1 acts through formation of complex with RbAp46 to stabilize RbAp46 protein. Overexpression of RbAp46 protein suppressed the NIH/3T3 cell growth induced by Ha-Ras(V12). SUMO-1 further enhances the suppression of cell growth through stabilization of RbAp46 protein. This is the first report to demonstrate that SUMO-1 can suppress Ras-related cell proliferation through stabilization of RbAp46 protein.
Mesh Terms:
Animals, Carrier Proteins, Cell Growth Processes, Cell Line, Humans, Immunoprecipitation, Mice, NIH 3T3 Cells, Nuclear Proteins, Retinoblastoma-Binding Protein 7, SUMO-1 Protein, Up-Regulation
Anticancer Res.
Date: Feb. 05, 2009
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