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The novel MMS‐inducible gene Mif1/KIAA0025 is a target of the unfolded protein response pathway
Author(s) -
van Laar Theo,
Schouten Theo,
Hoogervorst Esther,
van Eck Marga,
van der Eb Alex J.,
Terleth Carrol
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01253-9
Subject(s) - tunicamycin , unfolded protein response , endoplasmic reticulum , gene , microbiology and biotechnology , biology , complementary dna , genetics
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.