文章基本信息

标题：Activation of the unfolded protein response pathway causes ceramide accumulation in yeast and INS-1E insulinoma cells
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作者：Sharon Epstein ; Clare L. Kirkpatrick ; Guillaume A. Castillon 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2012
卷号：53
期号：3
页码：412-420
DOI：10.1194/jlr.M022186
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Sphingolipids are not only important components of membranes but also have functions in protein trafficking and intracellular signaling. The LCB1 gene encodes a subunit of the serine palmitoyltransferase, which is responsible for the first step of sphingolipid synthesis. Here, we show that activation of the unfolded protein response (UPR) can restore normal ceramide levels and viability in yeast cells with a conditional defect in LCB1 . Dependence on UPR was demonstrated by showing the HAC1 -dependence of the suppression. A similar induction of ceramides by UPR seems to take place in mammalian cells. In rat pancreatic INS-1E cells, UPR activation induces the transcription of the CerS6 gene, which encodes a ceramide synthase. This correlates with the specific accumulation of ceramide with a C16 fatty acyl chain upon UPR activation. Therefore, our study reveals a novel connection between UPR induction and ceramide synthesis that seems to be conserved between yeast and mammalian cells.
关键词：sphingolipids ; serine palmitoyltransferase ; endoplasmic reticulum stress ; CerS6 ; fatty acid hydroxylation