Regulation of the fission yeast transcription factor Pap1 by oxidative stress: requirement for the nuclear export factor Crm1 (Exportin) and the stress-activated MAP kinase Sty1/Spc1

被引:260
作者
Toone, WM
Kuge, S
Samuels, M
Morgan, BA
Toda, T
Jones, N
机构
[1] Imperial Canc Res Fund, Lab Gene Regulat, London WC2A 3PX, England
[2] Imperial Canc Res Fund, Lab Cell Regulat, London WC2A 3PX, England
[3] Univ Tokyo, Inst Med Sci, Minato Ku, Tokyo 108, Japan
[4] Newcastle Univ, Sch Med, Dept Biochem & Genet, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
关键词
MAP kinase; stress activation; oxidative stress; Pap1 transcription factor; regulated localization;
D O I
10.1101/gad.12.10.1453
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The fission yeast Sty1 stress-activated MAP kinase is crucial for the cellular response to a variety of stress conditions. Accordingly, sty1(-) cells are defective in their response to nutrient limitation, lose viability in stationary phase, and are hypersensitive to osmotic stress, oxidative stress, and UV treatment. Some of these phenotypes are caused by Sty1-dependent regulation of the Atf1 transcription factor, which controls both meiosis-specific and osmotic stress-responsive genes. However, in this report we demonstrate that the cellular response to oxidative stress and to treatment with a variety of cytotoxic agents is the result of Sty1 regulation of the Pap1 transcription factor, a bZip protein with structural and DNA binding similarities to the mammalian c-Jun protein. We show that both Sty1 and Pap1 are required for the expression of a number of genes involved in the oxidative stress response and for the expression of two genes, hba2(+)/bfr1(+) and pmd1(+), which encode energy-dependent transport proteins involved in multidrug resistance. Furthermore, rye demonstrate that Pap1 is regulated by stress-dependent changes in subcellular localization. On imposition of oxidative stress, the Pap1 protein relocalizes from the cytoplasm to the nucleus in a process that is dependent on the Sty1 kinase. This relocalization is the result of regulated protein export, rather than import, and involves the Crm1 (exportin) nuclear export factor and the dcd1(+)/pim1(+) gene that encodes an Ran nucleotide exchange factor.
引用
收藏
页码:1453 / 1463
页数:11
相关论文
共 70 条
[2]  
BAEUERLE PA, 1994, ANNU REV IMMUNOL, V12, P540
[3]   AN OSMOSENSING SIGNAL TRANSDUCTION PATHWAY IN YEAST [J].
BREWSTER, JL ;
DEVALOIR, T ;
DWYER, ND ;
WINTER, E ;
GUSTIN, MC .
SCIENCE, 1993, 259 (5102) :1760-1763
[4]   A mutation in a thioredoxin reductase homolog suppresses p53-induced growth inhibition in the fission yeast Schizosaccharomyces pombe [J].
Casso, D ;
Beach, D .
MOLECULAR & GENERAL GENETICS, 1996, 252 (05) :518-529
[5]  
CHIN KV, 1990, J BIOL CHEM, V265, P221
[7]  
Degols G, 1996, MOL CELL BIOL, V16, P2870
[8]   Discrete roles of the Spc1 kinase and the Atf1 transcription factor in the UV response of Schizosaccharomyces pombe [J].
Degols, G ;
Russell, P .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (06) :3356-3363
[9]   JNK1 - A PROTEIN-KINASE STIMULATED BY UV-LIGHT AND HA-RAS THAT BINDS AND PHOSPHORYLATES THE C-JUN ACTIVATION DOMAIN [J].
DERIJARD, B ;
HIBI, M ;
WU, IH ;
BARRETT, T ;
SU, B ;
DENG, TL ;
KARIN, M ;
DAVIS, RJ .
CELL, 1994, 76 (06) :1025-1037
[10]  
Fantes P., 1993, Experiments with Fission Yeast