The novel MMS-inducible gene Mif1/KIAA0025 is a target of the unfolded protein response pathway

被引：37

作者：

van Laar, T ^{[1
]}

Schouten, T ^{[1
]}

Hoogervorst, E ^{[1
]}

van Eck, M ^{[1
]}

van der Eb, AJ ^{[1
]}

Terleth, C ^{[1
]}

机构：

[1] Leiden Univ, Med Ctr, MGC Dept Radiat Genet & Chem Mutagenesis, NL-2300 RA Leiden, Netherlands

来源：

FEBS LETTERS | 2000年 / 469卷 / 01期

关键词：

unfolded protein response; tunicamycin; methyl methanesulfonate; osmotic shock; ubiquitin-like; BiP/GRP78;

D O I：

10.1016/S0014-5793(00)01253-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In a search for genes induced by DNA-damaging agents, we identified two genes that are activated by methyl methanesulfonate (MMS), Expression of both genes is regulated after endoplasmic reticulum (ER) stress via the unfolded protein response (UPR) pathway. The first gene of those identified is the molecular chaperone BiP/GRP78. The second gene, Mif1, is identical to the anonymous cDNA KIAA0025. Treatment with the glycosylation inhibitor tunicamycin both enhances the synthesis of Mif1 mRNA and protein. The Mif1 5' flanking region contains a functional ER stress-responsive element which is sufficient for induction by tunicamycin. MMS, on the other hand, activates Mif1 via an UPR-independent pathway. The gene encodes a 52 kDa protein with homology to the human DNA repair protein HHR23A and contains an ubiquitin-like domain. Overexpressed Mif1 protein is localized in the ER. (C) 2000 Federation of European Biochemical Societies.

引用

页码：123 / 131

页数：9

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