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首页> 外文期刊>Biochimica et Biophysica Acta. Gene Regulatory Mechanisms >ZNF509S1 downregulates PUMA by inhibiting p53K382 acetylation and p53-DNA binding
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ZNF509S1 downregulates PUMA by inhibiting p53K382 acetylation and p53-DNA binding

机译：ZNF509S1通过抑制p53K382乙酰化和P53-DNA结合来调整PUMA

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摘要

Abstract Expression of the POK family protein ZNF509L, and -its S1 isoform, is induced by p53 upon exposure to genotoxic stress. Due to alternative splicing of the ZNF509 primary transcript, ZNF509S1 lacks the 6 zinc-fingers and C-terminus of ZNF509L, resulting in only one zinc-finger. ZNF509L and -S1 inhibit cell proliferation by activating p21/CDKN1A and RB transcription, respectively. When cells are exposed to severe DNA damage, p53 activates PUMA ( p 53- u pregulated m odulator of a poptosis) transcription. Interestingly, apoptosis due to transcriptional activation of PUMA by p53 is attenuated by ZNF509S1. Thus we investigated the molecular mechanism(s) underlying the transcriptional attenuation and anti-apoptotic effects of ZNF509S1. We show that ZNF509S1 modulation of p53 activity is important in PUMA gene transcription by modulating post-translational modification of p53 by p300. ZNF509S1 directly interacts with p53 and inhibits p300-mediated acetylation of p53 lysine K382, with deacetylation of p53 K382 leading to decreased DNA binding at the p53 response element 1 of the PUMA promoter. ZNF509S1 may play a role not only in cell cycle arrest, by activating RB expression, but also in rescuing cells from apoptotic death by repressing PUMA expression in cells exposed to severe DNA damage. Highlights ? ZNF509S1 decreases apoptosis induced by severe DNA damage only in the presence of p53. ? ZNF509S1 represses PUMA gene transcription induced by etoposide. ? ZNF509S1 inhibits binding of p53 to the PUMA promoter via direct interaction with p53. ? ZNF509S1 modulates acetylation of p53 K382 by p300.
机译：摘要POK系列蛋白ZNF509L的表达，以及-TIS-its S1同种型在暴露于遗传毒性应激后诱导。由于ZNF509初级转录物的替代剪接，ZNF509S1缺乏ZNF509L的6个锌 - 手指和C-末端，导致仅一个锌手指。 ZnF5091和-S1分别通过激活P21 / CDKN1A和RB转录来抑制细胞增殖。当细胞暴露于严重的DNA损伤时，P53激活PUMA（p 53- Upregulated植物的Modulator）转录。有趣的是，P53对P53的转录激活引起的细胞凋亡由ZNF509S1衰减。因此，我们研究了ZNF509S1的转录衰减和抗凋亡作用的分子机制。我们表明，通过通过P300调节P53的翻译后修饰，P53活性的ZnF509S1调节在PUMA基因转录中是重要的。 ZnF509S1直接与P53相互作用，抑制P300介导的P53赖氨酸K382乙酰化，P53 K382的脱乙酰化导致P53响应元件1的DNA结合降低。通过激活RB表达，ZNF509S1不仅可以在细胞周期停滞中发挥作用，而且通过抑制暴露于严重DNA损伤的细胞中的PUMA表达，抑制来自凋亡死亡的细胞。强调 ？ ZNF509S1仅在P53存在下降低严重的DNA损伤诱导的细胞凋亡。还ZNF509S1抑制了依托泊苷诱导的PUMA基因转录。还ZnF509S1通过与P53的直接相互作用抑制P53与PUMA启动子的结合。还ZNF509S1通过P300调节P53 K382的乙酰化。

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    Bu-Nam Jeon; Jae-Hyeon Yoon; Dohyun Han; Min-Kyeong Kim; Youngsoo Kim; Seo-Hyun Choi; Jiyang Song; Kyung-Sup Kim; Kunhong Kim; Man-Wook Hur;

  • 作者单位

    Brain Korea 21 Plus Project for Medical Science Severance Biomedical Research Institute;

    Brain Korea 21 Plus Project for Medical Science Severance Biomedical Research Institute;

    Department of Biomedical Sciences and Biomedical Engineering Seoul National University College of;

    Brain Korea 21 Plus Project for Medical Science Severance Biomedical Research Institute;

    Department of Biomedical Sciences and Biomedical Engineering Seoul National University College of;

    Brain Korea 21 Plus Project for Medical Science Severance Biomedical Research Institute;

    Brain Korea 21 Plus Project for Medical Science Severance Biomedical Research Institute;

    Brain Korea 21 Plus Project for Medical Science Severance Biomedical Research Institute;

    Brain Korea 21 Plus Project for Medical Science Severance Biomedical Research Institute;

    Brain Korea 21 Plus Project for Medical Science Severance Biomedical Research Institute;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
  • 关键词

    ZNF509S1 (ZBTB49); p53; PUMA; Post-translational modification; Apoptosis;

    机译：ZNF509S1（ZBTB49）;P53;PUMA;翻译后修饰;细胞凋亡;

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