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

In a search for genes induced by DNA-damaging agents, we identified two gen es 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 a nonymous cDNA KIAA0025. Treatment with the glycosylation inhibitor tunicamy cin both enhances the synthesis of Mif1 mRNA and protein. The Mif1 5' flank ing region contains a functional ER stress-responsive element which is suff icient for induction by tunicamycin. MMS, on the other hand, activates Mif1 via an UPR-independent pathway. The gene encodes a 52 kDa protein with hom ology to the human DNA repair protein HHR23A and contains an ubiquitin-like domain. Overexpressed Mif1 protein is localized in the ER. (C) 2000 Federa tion of European Biochemical Societies.