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 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.
van Laar
T
T
MGC-Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Centre, P.O. Box 9503, 2300 RA, Leiden, The Netherlands.
Schouten
T
T
Hoogervorst
E
E
van Eck
M
M
van der Eb
A J
AJ
Terleth
C
C
D000595:Amino Acid Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004249:DNA Damage; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D008741:Methyl Methanesulfonate / Q000494:pharmacology*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D017510:Protein Folding; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D014415:Tunicamycin / Q000494:pharmacology
D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D018832:Molecular Chaperones; D012333:RNA, Messenger; D014415:Tunicamycin; C086985:RAD23A protein, human; D008741:Methyl Methanesulfonate; D045643:DNA Repair Enzymes