Hexosamine pathway and (ER) protein quality control

被引:54
作者
Denzel, Martin S. [1 ]
Antebi, Adam [1 ,2 ,3 ]
机构
[1] Max Planck Inst Biol Ageing, D-50931 Cologne, Germany
[2] Baylor Coll Med, Huffington Ctr Aging, Dept Mol & Cellular Biol, Houston, TX 77030 USA
[3] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50674 Cologne, Germany
关键词
EXTENDS LIFE-SPAN; O-GLCNACYLATION; CHEMICAL CHAPERONES; MOUSE MODEL; ACTIVATION; PHOSPHORYLATION; GLYCOSYLATION; BIOSYNTHESIS; STRESS; SITE;
D O I
10.1016/j.ceb.2014.10.001
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:14 / 18
页数:5
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