Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation
Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation
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DOI：
10.1016/s0092-8674(00)80835-1
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发表时间：
2000-04-28
期刊：
影响因子：
64.5
通讯作者：
Walter, P
中科院分区：
文献类型：
--
作者：
Travers, KJ;Patil, CK;Walter, P
未折叠蛋白反应(UPR)调节内质网(ER)中应激反应基因的表达。我们利用DNA微阵列确定了UPR的转录范围。UPR不像早期工作所预期的那样只调控内质网驻留的伴侣和磷脂的生物合成，而是影响多个内质网和分泌途径功能。对参与ER相关蛋白降解(ERAD)的UPR靶标的研究揭示了这些反应之间的密切协调：有效的ERAD需要完整的UPR，而UPR诱导增加ERAD的能力。相反，ERAD的丧失会导致结构性的UPR诱导。最后，ERAD和UPR的同时丢失大大降低了细胞的存活率。因此，UPR和ERAD是协调处理错误折叠的蛋白质所需的动态反应，即使在没有急性应激的情况下也是如此。
The unfolded protein response (UPR) regulates gene expression in response to stress in the endoplasmic reticulum (ER). We determined the transcriptional scope of the UPR using DNA microarrays. Rather than regulating only ER-resident chaperones and phospholipid biosynthesis, as anticipated from earlier work, the UPR affects multiple ER and secretory pathway functions. Studies of UPR targets engaged in ER-associated protein degradation (ERAD) reveal an intimate coordination between these responses: efficient ERAD requires an intact UPR, and UPR induction increases ERAD capacity. Conversely, loss of ERAD leads to constitutive UPR induction. Finally, simultaneous loss of ERAD and the UPR greatly decreases cell viability. Thus, the UPR and ERAD are dynamic responses required for the coordinated disposal of misfolded proteins even in the absence of acute stress.