Hexosamine pathway and (ER) protein quality control
Hexosamine pathway and (ER) protein quality control
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DOI：
10.1016/j.ceb.2014.10.001
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发表时间：
2015-04-01
影响因子：
7.5
通讯作者：
Antebi, Adam
中科院分区：
文献类型：
--
作者：
Denzel, Martin S.;Antebi, Adam
在己糖胺途径（HP）中产生的氨基糖用于蛋白质糖基化反应，所述反应涉及蛋白质成熟和细胞信号传导。最近的证据表明，HP在蛋白质质量控制和衰老中的作用。秀丽隐杆线虫中HP产物UDP-N-乙酰葡萄糖胺的升高导致对有毒易聚集蛋白质的抵抗力并延长寿命。谷氨酰胺-果糖-6-磷酸氨基转移酶（GFAT-1）是HP的关键酶，是未折叠蛋白反应（UPR）的靶标。因此，小鼠的心脏应激导致GFAT-1活化，其触发细胞保护反应。给老年小鼠喂食葡萄糖胺可以延长它们的预期寿命。在这里，我们讨论了HP激活和细胞蛋白质质量控制机制，导致抗应激和抑制年龄相关的蛋白毒性。
Aminosugars produced in the hexosamine pathway (HP) are utilized in protein glycosylation reactions involved in protein maturation and cellular signaling. Recent evidence revealed a role of the HP in protein quality control and ageing. Elevation of the HP product UDP-N-acetylglucosamine in the nematode Caenorhabditis elegans results in resistance towards toxic aggregation-prone proteins, and extended lifespan. Glutamine-fructose 6 phosphate aminotransferase (GFAT-1), the HP's key enzyme, is a target of the unfolded protein response (UPR). Thus, cardiac stress in mice results in GFAT-1 activation that triggers a cytoprotective response. Feeding of glucosamine to aged mice increases their life expectancy. Here we discuss HP activation and cellular protein quality control mechanisms that result in stress resistance and suppression of age-related proteotoxicity.