The ubiquitin-proteasome system regulates p53-mediated transcription at p21waf1 promoter.
The ubiquitin-proteasome system regulates p53-mediated transcription at p21waf1 promoter.
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泛素-蛋白酶体系统在 p21waf1 启动子处调节 p53 介导的转录。
作者：
Zhu,Q;Wani,G;Yao,J;Patnaik,S;Wang,Q-E;El-Mahdy,MA;Praetorius-Ibba,M;Wani,AA
泛素(Ub) -蛋白酶体系统（UPS）通过用Ub标签修饰靶蛋白来促进蛋白酶体降解。新出现的证据表明UPS在调节基因转录中的作用。在本研究中，我们提供了UPS参与肿瘤抑制因子p53转录激活功能的证据。我们发现泛素化和蛋白酶体功能都是p53介导的有效转录所必需的。放线菌素D、5,6 -二氯-1-β-D-核呋喃基-苯并咪唑或α-amanitin破坏转录可导致细胞p53蛋白的积累。MG132对蛋白酶体的抑制增加了p53蛋白在p53应答的p21 waf1启动子上的占据。此外，在体内和体外，19S蛋白酶体的Sug-1组分与p53有物理相互作用。此外，在紫外线诱导的DNA损伤下，19S蛋白酶体成分Sug1和S1都以类似于p53的动力学模式被募集到p21 waf1启动子区域。这些结果表明UPS正调控p21 waf1启动子上p53介导的转录。
The ubiquitin (Ub)–proteasome system (UPS) promotes the proteasomal degradation of target proteins by decorating them with Ub labels. Emerging evidence indicates a role of UPS in regulating gene transcription. In this study, we provided evidence for the involvement of UPS in the transcriptional activation function of tumor suppressor p53. We showed that both ubiquitylation and proteasomal functions are required for efficient transcription mediated by p53. Disruption of transcription by actinomycin D, 5, 6-dichloro-1-β-D-ribofuranosyl-benzimadazole or α-amanitin leads to accumulation of cellular p53 protein. Proteasome inhibition by MG132 increases the occupancy of p53 protein at p53-responsive p21 waf1 promoter. In addition, the Sug-1 component of 19S proteasome physically interacts with p53 in vitro and in vivo. Moreover, in response to ultraviolet-induced DNA damage, both the 19S proteasomal components, Sug1 and S1, are recruited to p21 waf1 promoter region in a kinetic pattern similar to that of p53. These results suggested that UPS positively regulates p53-mediated transcription at p21 waf1 promoter.