Inhibition of p53 deSUMOylation exacerbates puromycin aminonucleoside-induced apoptosis in podocytes.
Inhibition of p53 deSUMOylation exacerbates puromycin aminonucleoside-induced apoptosis in podocytes.
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DOI：
10.3390/ijms151121314
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发表时间：
2014-11-18
影响因子：
5.6
通讯作者：
Lin H
中科院分区：
文献类型：
--
作者：
Wang L;Zhu J;Fang M;Zhang T;Xie H;Wang N;Shen N;Guo H;Fu B;Lin H
细胞凋亡是足细胞数量减少的主要原因，这会导致蛋白尿和/或肾小球硬化。新的证据表明，去SUMO化是一种动态的翻译后修饰，它逆转了SUMO化，参与了Burkitt淋巴瘤细胞和心肌细胞的凋亡；然而，去SUMO化对足细胞凋亡的影响尚不清楚。P53蛋白在足细胞凋亡的发病机制中起主要作用，P53蛋白可以苏木糖化。因此，在本研究中，我们评估了由Sent rin/SUMO特异性蛋白水解酶1(SENP1)调控的P53去苏木酸化对足细胞凋亡的影响。我们的结果表明，SENP1缺乏显著增加了嘌呤霉素氨基核苷(PAN)诱导的足细胞凋亡。此外，在PAN刺激过程中，SENP1基因敲除导致足细胞中SUMO化的P53蛋白积聚，并导致P53靶基因Bax、Noxa和PUMA表达增加。因此，SENP1可能是防止足细胞凋亡所必需的，至少部分是通过去SUMO来调节P53蛋白的功能。对去SUMO的调控可能为涉及足细胞凋亡的肾小球疾病的治疗提供新的策略。
Apoptosis is a major cause of reduced podocyte numbers, which leads to proteinuria and/or glomerulosclerosis. Emerging evidence has indicated that deSUMOylation, a dynamic post-translational modification that reverses SUMOylation, is involved in the apoptosis of Burkitt’s lymphoma cells and cardiomyocytes; however, the impact of deSUMOylation on podocyte apoptosis remains unexplored. The p53 protein plays a major role in the pathogenesis of podocyte apoptosis, and p53 can be SUMOylated. Therefore, in the present study, we evaluated the effect of p53 deSUMOylation, which is regulated by sentrin/SUMO-specific protease 1 (SENP1), on podocyte apoptosis. Our results showed that SENP1 deficiency significantly increases puromycin aminonucleoside (PAN)-induced podocyte apoptosis. Moreover, SENP1 knockdown results in the accumulation of SUMOylated p53 protein and the increased expression of the p53 target pro-apoptotic genes, BAX, Noxa and PUMA, in podocytes during PAN stimulation. Thus, SENP1 may be essential for preventing podocyte apoptosis, at least partly through regulating the functions of p53 protein via deSUMOylation. The regulation of deSUMOylation may provide a novel strategy for the treatment of glomerular disorders that involve podocyte apoptosis.
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影响因子：
20.1
作者：
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