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首页> 外文期刊>Molecular and Cellular Biology >Human BAG-1 Proteins Bind to the Cellular Stress Response Protein GADD34 and Interfere with GADD34 Functions
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Human BAG-1 Proteins Bind to the Cellular Stress Response Protein GADD34 and Interfere with GADD34 Functions

机译：人BAG-1蛋白与细胞应激反应蛋白GADD34结合并干扰GADD34功能

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The cellular stress response protein GADD34 mediates growth arrest and apoptosis in response to DNA damage, negative growth signals, and protein malfolding. GADD34 binds to protein phosphatase PP1 and can attenuate the translational elongation of key transcriptional factors through dephosphorylation of eukaryotic initiation factor 2α (eIF2α). Recently, we reported the involvement of human SNF5/INI1 (hSNF5/INI1) protein in the functions of GADD34 and showed that hSNF5/INI1 binds GADD34 and stimulates the bound PP1 phosphatase activity. To better understand the regulatory and functional mechanisms of GADD34, we undertook a yeast two-hybrid screen with full-length GADD34 as bait in order to identify additional protein partners of GADD34. We report here that human cochaperone protein BAG-1 interacts with GADD34 in vitro and in SW480 cells treated with the proteasome inhibitor z-LLL-B to induce apoptosis. Two other proteins, Hsp70/Hsc70 and PP1, associate reversibly with the GADD34-BAG-1 complex, and their dissociation is promoted by ATP. BAG-1 negatively modulates GADD34-bound PP1 activity, and the expression of BAG-1 isoforms can also mask GADD34-mediated inhibition of colony formation and suppression of transcription. Our findings suggest that BAG-1 may function to suppress the GADD34-mediated cellular stress response and support a role for BAG-1 in the survival of cells undergoing stress.
机译：细胞应激反应蛋白GADD34响应DNA损伤，负增长信号和蛋白折叠而介导生长停滞和凋亡。 GADD34与蛋白质磷酸酶PP1结合，并可以通过真核起始因子2α（eIF2α）的去磷酸化作用来减弱关键转录因子的翻译延伸。最近，我们报道了人类SNF5 / INI1（hSNF5 / INI1）蛋白参与GADD34的功能，并显示hSNF5 / INI1结合GADD34并刺激了结合的PP1磷酸酶活性。为了更好地了解GADD34的调控和功能机制，我们进行了以全长GADD34为诱饵的酵母双杂交筛选，以鉴定GADD34的其他蛋白伴侣。我们在这里报告人类伴侣蛋白BAG-1与GADD34在体外相互作用，并在用蛋白酶体抑制剂z-LLL-B处理的SW480细胞中诱导凋亡。 Hsp70 / Hsc70和PP1这两个其他蛋白质可逆地与GADD34-BAG-1复合物缔合，并且它们的解离作用由ATP促进。 BAG-1负调节GADD34绑定的PP1活性，BAG-1同工型的表达也可以掩盖GADD34介导的菌落形成抑制和转录抑制。我们的发现表明BAG-1可能起到抑制GADD34介导的细胞应激反应的作用，并支持BAG-1在遭受应激的细胞存活中的作用。

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