TOPK 通过调控 SIRT1/p53 抑制 TNF-α诱导的颗粒细胞凋亡。
TOPK inhibits TNF-α-induced granulosa cell apoptosis via regulation of SIRT1/p53.
机构信息
Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, South Korea.
Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, South Korea.
出版信息
Biochem Biophys Res Commun. 2023 Jul 5;664:128-135. doi: 10.1016/j.bbrc.2023.04.113. Epub 2023 Apr 29.
T-LAK cell originated protein kinase (TOPK) has been shown to regulate proliferation, invasion or migration of various cancer cells. However, the role of TOPK in follicle environments remains unknown. Here we reveal that TOPK inhibits TNF-α-induced human granulosa COV434 cell apoptosis. The expression of TOPK were increased in COV434 cells in response to TNF-α. TOPK inhibition also decreased TNF-α-induced SIRT1 expression but promoted TNF-α-induced p53 acetylation and expression of PUMA or NOXA. Accordingly, TOPK inhibition attenuated TNF-α-mediated SIRT1 transcriptional activity. In addition, SIRT1 inhibition augmented acetylation of p53 or expression of PUMA and NOXA in response to TNF-α, leading to COV434 cell apoptosis. We conclude that TOPK suppresses TNF-α-induced COV434 granulosa cell apoptosis via regulation of p53/SIRT1 axis, suggesting a potential role of TOPK in regulation of ovarian follicular development.
T-LAK 细胞源蛋白激酶 (TOPK) 已被证明可调节各种癌细胞的增殖、侵袭或迁移。然而，TOPK 在卵泡环境中的作用尚不清楚。在这里，我们揭示 TOPK 抑制 TNF-α 诱导的人颗粒细胞 COV434 细胞凋亡。TOPK 的表达在 TNF-α 刺激的 COV434 细胞中增加。TOPK 抑制也降低了 TNF-α 诱导的 SIRT1 表达，但促进了 TNF-α 诱导的 p53 乙酰化和 PUMA 或 NOXA 的表达。因此，TOPK 抑制减弱了 TNF-α 介导的 SIRT1 转录活性。此外，SIRT1 抑制增加了 TNF-α 反应中 p53 或 PUMA 和 NOXA 的乙酰化，导致 COV434 细胞凋亡。我们得出结论，TOPK 通过调节 p53/SIRT1 轴抑制 TNF-α 诱导的 COV434 颗粒细胞凋亡，提示 TOPK 在调节卵巢卵泡发育中具有潜在作用。
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