The Oligomerization Of SENP3 And The Roles Of SENP3 In Response To Oxidative Stress

SENP3 is a member of Sentrin/SUMO-specific proteases(SENPs) family which play an important regulatory role in cell functions and cell cycle, cell proliferation, cell differentiation by deSUMOylating its target proteins. In this study, we explored that a new role in response to oxidative stress and discovered a new property of oligomerization.In the first part of the study, we showed interest to the responses of SENP3 upon different level of oxidative stress. We first found that SENP3 could selectively upregulate gene expression of some antioxidases via the inhibition of protein degradation and the translocation from nucleolus to nucleoplasm. It sheds light on the role of SENP3 in the cellular redox regulation.In the second part, we explored the mechanism and the effects of SENP3 translocation under cellular stress. Using the method of the Time lapse of laser scanning confocal microscope and other image techniques, we found that SENP3 translocated from nucleolus to nucleoplasm under various cellular stresses in a redox dependent manner. There was the direct evidence that SENP3 would translocate while the cells was treated with different dose of H2O2(hydrogen peroxide). Further, we constructed some truncations and then mutated the cysteines to find the main site which was sensitive to the oxidative stress. The results showed that the SENP3 Cys532 was implicated to be oxidized in response to the cellular redox stat. And then, we detected the the interaction of SENP3 with its substrate proteins followed by the translocation of SENP3, showing increase interaction with nucleoplasmic p53, stable interaction with PELP1 and decrease interaction with B23. Taken together, oxidative modification of SENP3 led to alteration of compartmental localization and in turn changed the function.In the third part, we explored the property of SENP3 oligomerization. Using the method of co-immunoprecipitation to test the interaction of different tagged SENP3, we found that SENP3 might be oligomerization. Further we mapped the sequence of 72-163 of SENP3 to be responsible to oligomerization. Of note, the cellular redox status had mild influence to the oligomerization of SENP3.