title: Int6/eIF3e promotes general translation and Atf1 abundance to modulate Sty1 MAPK-dependent stress response in fission yeast.
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.
authors.affiliation: Molecular Cellular and Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, Kansas 66506, USA.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Udagawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Nemoto
authors.forename: Caroline R M
authors.initials: CR
authors.lastname: Wilkinson
authors.forename: Jana
authors.initials: J
authors.lastname: Narashimhan
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Stephen
authors.initials: S
authors.lastname: Watt
authors.forename: Aaron
authors.initials: A
authors.lastname: Zook
authors.forename: Nic
authors.initials: N
authors.lastname: Jones
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Wek
authors.forename: Jürg
authors.initials: J
authors.lastname: Bähler
authors.forename: Katsura
authors.initials: K
authors.lastname: Asano
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000640:Amitrole / Q000494:pharmacology; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D006639:Histidine / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D005810:Multigene Family; D009154:Mutation; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000187:drug effects / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000596:Amino Acids; D039621:Eukaryotic Initiation Factor-3; D011506:Proteins; D029702:Schizosaccharomyces pombe Proteins; D006639:Histidine; C079238:alcohol O-acetyltransferase; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe; D000640:Amitrole