A role for SIR-2.1 regulation of ER stress response genes in determining C-elegans life span
A role for SIR-2.1 regulation of ER stress response genes in determining C-elegans life span
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DOI：
10.1016/j.devcel.2005.09.017
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发表时间：
2005-11-01
影响因子：
11.8
通讯作者：
Guarente, L
中科院分区：
文献类型：
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作者：
Viswanathan, M;Kim, SK;Guarente, L
秀丽线虫SIR-2.1是NAD(+)依赖的蛋白脱乙酰酶SIR-2家族的成员，已被证明通过胰岛素/IGF途径转录因子daf-16调节线虫衰老。然而，用小分子白藜芦醇治疗线虫，可以延长寿命，完全依赖于SIR-2.1，但不依赖于DAF-16。对白藜芦醇处理的蠕虫进行的微阵列分析表明，编码类病毒谷氨酰胺/天冬酰胺富含蛋白的基因家族在转录上被诱导，这些基因参与了包膜质网(ER)对未折叠蛋白的应激反应。该内质网应激基因家族成员ABU-11的RNA干扰可阻断白藜芦醇介导的寿命延长，过表达ABU-11可延长转基因动物的寿命。此外，SIR-2.1通常抑制ABU-11和其他ER应激基因家族成员的转录，表明白藜芦醇通过抑制SIR-2.1介导的ER应激基因的抑制而延长生命。我们的发现表明，ABU-11及其内质网应激基因家族的其他成员是线虫寿命的积极决定因素。
C. elegans SIR-2.1, a member of the Sir-2 family of NAD(+)-dependent protein deacetylases, has been shown to regulate nematode aging via the insulin/IGF pathway transcription factor daf-16. Treatment of C. elegans with the small molecule resveratrol, however, extends life span in a manner fully dependent upon sir-2.1, but independent of daf-16. Microarray analysis of worms treated with resveratrol demonstrates the transcriptional induction of a family of genes encoding prion-like glutamine/asparagine-rich proteins involved in encloplasmic reticulum (ER) stress response to unfolded proteins. RNA interference of abu-11, a member of this ER stress gene family, abolishes resveratrol-mediated life span extension, and overexpression of abu-11 extends the life span of transgenic animals. Furthermore, SIR-2.1 normally represses transcription of abu-11 and other ER stress gene family members, indicating that resveratrol extends life span by inhibiting sir-2.1-mediated repression of ER stress genes. Our findings demonstrate that abu-11 and other members of its ER stress gene family are positive determinants of C. elegans life span.