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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Control of p53 multimerization by Ubc13 is JNK-regulated
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Control of p53 multimerization by Ubc13 is JNK-regulated

机译：Ubc13对p53多聚体的控制受JNK调控

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摘要

The p53 tumor suppressor protein is a key regulator of cellular proliferation and survival whose function is tightly regulated at the levels of transcription and protein stability. Here, we unveil the fine control of p53 on translationally active polysomes. We have previously reported that Ubc13, an E2 ubiquitin-conjugating enzyme, directly regulates p53 localization and transcriptional activity. We now demonstrate that the association of p53 and Ubc13 on polysomes requires ongoing translation and results in p53 ubiquitination that interferes with its tetramerization. JNK phosphorylation of p53 at Threonine 81 occurring on polysomes is required for the dissociation of Ubc13 from p53, leading to p53 multimerization and transcriptional activation. Inhibition of JNK activity or expression of a nonphosphorylatable mutant of p53 maintains an Ubc13-p53 complex that inhibits p53 multimerization. Our findings reveal a layer in the regulation of pS3 multimerization that requires the concerted action of JNK and Ubc13 on polysome-bound p53.
机译：p53肿瘤抑制蛋白是细胞增殖和存活的关键调节剂，其功能在转录和蛋白稳定性水平上受到严格调节。在这里，我们揭示了对翻译活性多核糖体上p53的精细控制。我们以前曾报道过，Eb泛素结合酶Ubc13直接调节p53的定位和转录活性。现在，我们证明p53和Ubc13在多核糖体上的缔合需要持续的翻译，并导致p53泛素化，从而干扰其四聚化。 Ubc13与p53的解离需要多核糖体上苏氨酸81上p53的JNK磷酸化，从而导致p53多聚化和转录激活。 JNK活性的抑制或p53的不可磷酸化突变体的表达维持了抑制p53多聚的Ubc13-p53复合物。我们的发现揭示了调控pS3多聚化的过程，这需要JNK和Ubc13对多核糖体结合的p53的协同作用。

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    Ivan Topisirovic; Gustavo J. Gutierrez; Meifan Chen; Ettore Appella; Katherine L. B. Borden; Zeev A. Ronai;

  • 作者单位

    Institute for Research in Immunology and Cancer, Universite de Montreal, Montreal, Quebec, H3T 1J4, Canada;

    Signal Transduction Program, Cancer Center, Burnham Institute for Medical Research, La Jolla, CA 92037;

    Signal Transduction Program, Cancer Center, Burnham Institute for Medical Research, La Jolla, CA 92037;

    Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;

    Institute for Research in Immunology and Cancer, Universite de Montreal, Montreal, Quebec, H3T 1J4, Canada Department of Pathology and Cell Biology, Universite de Montreal, Montreal, Quebec, H3T 1J4, Canada;

    Signal Transduction Program, Cancer Center, Burnham Institute for Medical Research, La Jolla, CA 92037 Signal Transduction Program, Burnham Institute for Medical Research, 10901 North Torrey Pines Rd., La Jolla, CA 92037;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    polysomes; ubiquitin;

    机译：多核糖体泛素;

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