SUMO2 modification of Aurora B and its impact on follicular development and atresia in the mouse ovary.

Abstract

In the mammalian ovary, >99% follicles fail to ovulate due to apoptosis in granulosa cells. Aurora B, a core subunit enzyme of the chromosomal passenger complex, exerts a crucial role in microtubule-kinetochore attachment, and has been reported to be modified by small ubiquitin-related modifier (SUMO) proteins. However, the details of how Aurora B and its SUMOylation impact on follicular development have yet to be fully elucidated. The aim of the present study was to explore the roles, and possible molecular mechanism, of Aurora B and its SUMOylation in the granulosa cells of the mouse follicle. It was revealed that the protein level of Aurora B increased with follicular development and the growth of the granulosa cells. Aurora B impacted follicular development and atresia through mediating the p38 mitogen-activated protein kinase and FasL/Fas pathways, and caused the down-regulation of cyclin-dependent kinase 4, proliferating cell nuclear antigen, Bcl-2, and upregulation of caspases-3 and -8 to modulate the viability of the granulosa cells. In addition, Aurora B undergoes modification by SUMO2, but not by SUMO1, in vivo and in vitro, and Lys-207 is a major modification site. SUMOylation modulates follicular development through an increase in Aurora B localization in the nucleus, and by stabilizing the protein level of Aurora B and keeping the viability of the granulosa cells. Taken together, Aurora B and its SUMOylation are important for follicular development and atresia in the ovaries of mice.