SUMO-specific proteases and the cell cycle. An essential role for SENP5 in cell proliferation

Post-translational modification by SUMO is a dynamic and reversible process and several SUMO-specific proteases that remove SUMO from substrates have been identified. We have recently described the activities of a new SUMO-specific protease, SENP5. We found that SENP5 discriminates between SUMO-1 and SUMO-2/3 and cells depleted of SENP5 by RNAi failed to proliferate. Our findings support the idea that differential substrate selection by the mammalian SUMO-specific proteases underlies their regulation of distinct biological processes. Furthermore, our finding of a nonredundant function for SENP5 in cell proliferation provides further support for the model that, analogous to phosphorylation, cycles of SUMOylation and deSUMOylation regulate orderly progression through cell division.