RRC ID 12678
Author Udagawa T, Nemoto N, Wilkinson CR, Narashimhan J, Jiang L, Watt S, Zook A, Jones N, Wek RC, Bähler J, Asano K.
Title Int6/eIF3e promotes general translation and Atf1 abundance to modulate Sty1 MAPK-dependent stress response in fission yeast.
Journal J. Biol. Chem.
Abstract int-6 is one of the frequent integration sites for mouse mammary tumor viruses. Although its product is the e-subunit of translation initiation factor eIF3, other evidence indicates that it interacts with proteasomes or other proteins to regulate protein stability. Here we report that the fission yeast int6(+) is required for overcoming stress imposed by histidine starvation, using the drug 3-aminotriazole (3AT). Microarray and complementary Northern studies using wild-type, int6Delta or gcn2Delta mutants indicate that 3AT-treated wild-type yeast induces core environmental stress response (CESR) genes in addition to typical general amino acid control (GAAC) genes whose transcription depends on the eIF2 kinase, Gcn2. In agreement with this, Sty1 MAPK and its target transcription factor Atf1, which signal the CESR, are required for overcoming 3AT-induced starvation. We find that Int6 is required for maintaining the basal level of Atf1 and for rapid transcriptional activation of the CESR on 3AT-insult. Pulse labeling experiments indicate that int6Delta significantly slows down de novo protein synthesis. Moreover, Atf1 protein half-life was reduced in int6Delta cells. These effects would account for the compromised Atf1 activity on 3AT-induced stress. Thus, the robust protein synthesis promoted by intact eIF3 appears to be a part of the requisites for sound Sty1 MAPK-dependent signaling governed by the activity of the Atf1 transcription factor.
Volume 283(32)
Pages 22063-75
Published 2008-8-8
DOI 10.1074/jbc.M710017200
PII M710017200
PMID 18502752
PMC PMC2494926
MeSH Amino Acids / metabolism Amitrole / pharmacology Eukaryotic Initiation Factor-3 / genetics Eukaryotic Initiation Factor-3 / metabolism* Gene Expression Profiling Gene Expression Regulation, Fungal* Histidine / metabolism Mitogen-Activated Protein Kinases / metabolism* Multigene Family Mutation Protein Biosynthesis* Proteins / genetics Proteins / metabolism* Schizosaccharomyces / drug effects Schizosaccharomyces / metabolism* Schizosaccharomyces pombe Proteins / metabolism* Signal Transduction
IF 4.011
Times Cited 18
Yeast ?