SUMOylation of mouse p53b by SUMO-1 promotes its pro-apoptotic function in ovarian granulosa cells.
SUMOylation of mouse p53b by SUMO-1 promotes its pro-apoptotic function in ovarian granulosa cells.
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DOI：
10.1371/journal.pone.0063680
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Huo LJ
中科院分区：
文献类型：
--
作者：
Liu XM;Yang FF;Yuan YF;Zhai R;Huo LJ
卵泡闭锁是哺乳动物卵巢中卵泡自发降解，阻碍生长和发育的过程。以往的研究表明，卵泡闭锁是由颗粒细胞凋亡引起的，许多与颗粒细胞凋亡相关的基因已经被鉴定出来。p53在小鼠颗粒细胞凋亡中的作用及其翻译后修饰尚不清楚。本研究的主要目的是探讨p53在小鼠颗粒细胞中的作用。我们发现，小鼠p53 b，而不是p53 a，可以SUMO-1的赖氨酸375，这是必不可少的蛋白质的稳定性，p53 b的剂量依赖性的方式。免疫荧光染色显示野生型p53 b定位于颗粒细胞核，而其SUMO化位点突变（K375 R）定位于细胞核和细胞质，提示SUMO化是p53 b在颗粒细胞核定位所必需的。野生型p53 b的过表达（而非SUMO化位点（K375 R）的突变）可显著诱导卵巢颗粒细胞凋亡相关基因Bax的表达，并增加颗粒细胞的凋亡水平。这表明SUMO-1对p53 b的修饰对于诱导颗粒细胞凋亡是必需的。我们的研究结果提供了强有力的证据表明，SUMO-1对p53 b的赖氨酸375处的修饰是其诱导小鼠颗粒细胞凋亡的活性所必需的，并且它参与了p53 b蛋白稳定性和核定位的调节。提示SUMO-1对p53 b的修饰可能通过诱导小鼠卵巢颗粒细胞凋亡来调节卵泡闭锁。
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.
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影响因子：
11.4
作者：
Gostissa, M;Hengstermann, A;Del Sal, G
通讯作者：
Del Sal, G
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