Null mutation in IRE1 gene inhibits overproduction of microsomal cytochrome P450Alk1 (CYP 52A3) and proliferation of the endoplasmic reticulum in Saccharomyces cerevisiae.
Overproduction of microsomal cytochrome P450Alk1 (P450Alk1) of Candida maltosa in Saccharomyces cerevisiae resulted in an extensive proliferation of endoplasmic reticulum (ER) and induction of Kar2p and Pdi1p. The ire1 null mutation severely suppressed ER proliferation, reduced the level of functional P450Alk1, and showed no induction of these ER chaperones, suggesting that the function of Ire1p is required for ER proliferation upon the overproduction of P450Alk1. Cerulenin, a potent inhibitor of lipid biosynthesis, also induced these chaperones in an Ire1p-dependent manner and limited the production of functional P450Alk1. These results imply that Ire1p may function to restore the balance between membrane proteins and lipids of the ER when the ER is relatively overcrowded by membrane proteins.
Department of Biotechnology The University of Tokyo, Bunkyo-ku, Tokyo, 113-8657, Japan.
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Takewaka
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Zimmer
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Hirata
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Ohta
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Takagi
D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D008854:Microscopy, Electron; D006899:Mixed Function Oxygenases / Q000096:biosynthesis / Q000235:genetics*; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins
D005656:Fungal Proteins; D008562:Membrane Glycoproteins; D029701:Saccharomyces cerevisiae Proteins; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C116330:CYP52A3 protein, Candida maltosa; D011494:Protein Kinases; C082863:IRE1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases