The E3 SUMO ligase PIASy is a regulator of cellular senescence and apoptosis (Retracted article. See vol. 80, pg. 1140, 2020)
The E3 SUMO ligase PIASy is a regulator of cellular senescence and apoptosis (Retracted article. See vol. 80, pg. 1140, 2020)
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DOI：
10.1016/j.molcel.2006.05.016
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发表时间：
2006-06-23
期刊：
影响因子：
16
通讯作者：
Dejean, Anne
中科院分区：
文献类型：
--
作者：
Bischof, Oliver;Schwamborn, Klaus;Dejean, Anne
细胞衰老和凋亡已经发展到抑制潜在致瘤细胞的不必要的增殖。在这里，我们表明，E3 SUMO连接酶PIASy在正常人成纤维细胞的过度表达招募p53和Rb肿瘤抑制通路，以引起衰老停滞。相反，在Rb缺陷的成纤维细胞中，PIASy的表达导致p53依赖性细胞凋亡。衰老的诱导需要PIASy E3活性，并且对皮亚斯连接酶家族的该成员具有特异性。PIASy刺激p53的类小泛素化和转录活性，并通过募集E2F应答启动子增加Rb依赖性共抑制。病毒癌蛋白E6抑制PIASy诱导的衰老和PIASy底物的SUMO化。最后，我们表明，缺乏PIASy的成纤维细胞表现出高度降低的倾向，经历衰老，响应于衰老刺激。总之，这些数据提供了第一个证据，E3 SUMO连接酶的直接作用，并通过暗示的SUMO途径，在细胞衰老和凋亡。
Cellular senescence and apoptosis have evolved to restrain unwarranted proliferation of potentially tumorigenic cells. Here we show that overexpression of the E3 SUMO ligase PIASy in normal human fibroblasts recruits the p53 and Rb tumor suppressor pathways to provoke a senescence arrest. By contrast, in Rb-deficient fibroblasts, expression of PIASy leads to p53-dependent apoptosis. Induction of senescence requires PIASy E3 activity and is specific for this member of the PIAS ligase family. PIASy stimulates sumoylation and transcriptional activity of p53 and increases Rb-dependent corepression through recruitment to E2F-responsive promoters. Viral oncoprotein E6 suppresses both PIASy-induced senescence and sumoylation of PIASy substrates. Finally, we show that fibroblasts lacking PIASy exhibit a highly reduced propensity to undergo senescence in response to a prosenescence stimulus. Altogether, these data provide the first evidence for a direct role of an E3 SUMO ligase, and by implication of the SUMO pathway, in cellular senescence and apoptosis.