title: SUMOylation of mouse p53b by SUMO-1 promotes its pro-apoptotic function in ovarian granulosa cells.
abstract: Follicular atresia is a process of spontaneous degradation of follicles, hindering growth and development in the mammalian ovary. Previous studies showed that follicular atresia was caused by apoptosis of granulosa cells, for which a number of apoptosis-related genes have already been identified. The roles of p53 in apoptosis of mouse granulosa cells and its post-translational modification are still unclear. The main objective of this study was to explore the roles of p53 in mouse granulosa cells. We found that mouse p53b, but not p53a, could be SUMOylated by SUMO-1 at lysine 375, which was essential for the protein stability of p53b in a dose-dependent manner. Immunofluorescent staining showed that wild p53b was located in the nucleus of granulosa cells, while its mutation of SUMOylated site (K375R) was localized in both nucleus and cytoplasm, implying that SUMOylation was necessary for the nuclear localization of p53b in granulosa cells. Overexpression of wild-type p53b, but not the mutation of SUMOylation site (K375R), significantly induced the expression of apoptosis-related gene, Bax, and increased the level of apoptosis in granulosa cells. This suggested that SUMO-1 modification of p53b was essential for inducing apoptosis in granulosa cells. Our results provide strong evidences that modification of p53b by SUMO-1 at lysine 375 was necessary for its activity to induce apoptosis in mouse granulosa cells, and it was involved in the regulation of p53b protein stability and nuclear localization. This implies that modification of p53b by SUMO-1 might regulate follicular atresia by inducing the apoptosis of ovarian granulosa cells in mice.
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, People's Republic of China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Liu
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Yang
authors.forename: Yi-Feng
authors.initials: YF
authors.lastname: Yuan
authors.forename: Rui
authors.initials: R
authors.lastname: Zhai
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Huo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D025842:SUMO-1 Protein / Q000378:metabolism*; D058207:Sumoylation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D025842:SUMO-1 Protein; D016159:Tumor Suppressor Protein p53