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posh is involved in Eiger-Basket (TNF-JNK) signaling and embryogenesis in Drosophila

Journal of Genetics and Genomics 2010年第9期37卷 605-619页

作者： Ming Zhang Yongqing Zhang Zhiheng Xu Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing 100101 China Graduate School Chinese Academy of Sciences Beijing 100039 China

TNFα can trigger different signaling pathways, including the JNK pathway, to regulate various biological functions such as cell death, differentiation and proliferation. The scaffold protein posh （Plenty of SH3 Domains） has been shown to be an important regulator of the JNK pathway, but whether it is involved in TNF-signaling has not been reported. Although posh has been implicated to play a role in development in zebrafish, it has not been studied in null mutants and the underlying mechanism of its effects is still not clear. In this study, we provide evidence that the JNK pathway scaffold protein, posh, is involved in TNF （Eiger） signaling in Drosophila. posh is likely to act downstream of dTAB2 and upstream of dTAK1 in the TNF-JNK signaling pathway. In addition, we found that posh is essential during Drosophila embryogenesis, including epidermal dorsal closure, similar to other JNK pathway components such as Silpper, Hemipterous, and Basket. We observed defects in F-actin accumulation and adherens junction formation during dorsal closure in different posh null mutants, suggesting that posh is required for epidermal cell migration and cell-shape change during epidermal dorsal closure.

关键词： TNF JNK posh embryogenesis cell migration adherents junction

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Regulation of the protein stability of posh and MLK family

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Protein & Cell 2010年第9期1卷 871-878页

作者： Chunyan Wang Yang Tao Yaqing Wang Zhiheng Xu Key Laboratory of Molecular and Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

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 *** components are organized by a scaffold protein,posh(Plenty of SH3’s),to ensure the effective activation of the JNK pathway and cell death upon apoptotic *** have shown recently that the expression of posh and MLK family proteins are regulated through protein *** 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 *** addition,posh’s ability to induce apoptosis is correlated with its stability as well as its MLK binding *** family’s stability,like that of posh,requires activation of ***,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.

关键词： the JNK pathway protein stability posh MLK family and poptosis

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