Regulation of the protein stability of POSH and MLK family

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• 作者：Chunyan Wang (1)
  Yang Tao (1)
  Yaqing Wang (1)
  Zhiheng Xu (1)
  
• 关键词：the JNK pathway ; protein stability ; POSH ; MLK family and poptosis
• 刊名：Protein & Cell
• 出版年：2010
• 出版时间：September 2010
• 年：2010
• 卷：1
• 期：9
• 页码：871-878
• 全文大小：337KB
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• 作者单位：Chunyan Wang (1)
  Yang Tao (1)
  Yaqing Wang (1)
  Zhiheng Xu (1)
  
  1. Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
  

文摘

Sequential activation of the JNK pathway components, including Rac1/Cdc42, MLKs (mixed-lineage kinases), MKK4/7 and JNKs, plays a required role in many cell death paradigms. Those components are organized by a scaffold protein, POSH (Plenty of SH3-/span>s), to ensure the effective activation of the JNK pathway and cell death upon apoptotic stimuli. We have shown recently that the expression of POSH and MLK family proteins are regulated through protein stability. By generating a variety of mutants, we provide evidence here that the Nterminal half of POSH is accountable for its stability regulation and its over-expression-induced cell death. In addition, POSH’s ability to induce apoptosis is correlated with its stability as well as its MLK binding ability. MLK family’s stability, like that of POSH, requires activation of JNKs. However, we were surprised to find out that the widely used dominant negative (d/n) form of c-Jun could down-regulate MLK’s stability, indicating that peptide from d/n c-Jun can be potentially developed into a therapeutical drug.