Dynamic O-GlcNAc modification of nucleocytoplasmic proteins in response to stress -: A survival response of mammalian cells
Dynamic O-GlcNAc modification of nucleocytoplasmic proteins in response to stress -: A survival response of mammalian cells
复制标题
DOI：
10.1074/jbc.m403773200
复制
发表时间：
2004-07-16
影响因子：
4.8
通讯作者：
Hart, GW
中科院分区：
文献类型：
--
作者：
Zachara, NE;O'Donnell, N;Hart, GW
细胞对环境、生理或化学应激的反应是损伤或疾病后存活的关键。在这里，我们描述了一种独特的信号机制，细胞通过该机制检测并响应压力，以求生存。各种各样的应激刺激迅速增加O-连接的β-N-乙酰氨基葡萄糖(O-GlcNAc)对核质蛋白的修饰，O-GlcNAc是后生动物丝氨酸和苏氨酸残基的一种必不可少的翻译后修饰。阻止或减少这种翻译后修饰会使细胞对压力更加敏感，导致细胞存活率下降；增加O-GlcNAc水平可以保护细胞。O-GlcNAc调节应激诱导的热休克蛋白诱导的速度和程度，为这些发现提供了分子基础。
Cellular response to environmental, physiological, or chemical stress is key to survival following injury or disease. Here we describe a unique signaling mechanism by which cells detect and respond to stress in order to survive. A wide variety of stress stimuli rapidly increase nucleocytoplasmic protein modification by O-linked beta-N-acetylglucosamine (O-GlcNAc), an essential post-translational modification of Ser and Thr residues of metazoans. Blocking this post-translational modification, or reducing it, renders cells more sensitive to stress and results in decreased cell survival; and increasing O-GlcNAc levels protects cells. O-GlcNAc regulates both the rates and extent of the stress-induced induction of heat shock proteins, providing a molecular basis for these findings.