FCCC LOGO Faculty Publications
Cohen TJ , Lee K , Rutkowski LH , Strich R
Ask10p mediates the oxidative stress-induced destruction of the Saccharomyces cerevisiae C-type cyclin Ume3p/Srb11p
Eukaryotic Cell. 2003 Oct;2(5) :962-970
Back to previous list
Srb11p-Srb10p is the budding yeast C-type cyclin-cyclin-dependent kinase that is required for the repression of several stress response genes. To relieve this repression, Srb11p is destroyed in cells exposed to stressors, including heat shock and oxidative stress. In the present study, we identified Ask10p (for activator of Skn7) by two-hybrid analysis as an interactor with Srb11p. Coimmunoprecipitation studies confirmed this association, and we found that, similar to Srb11p-Srb10p, Ask10p is a component of the RNA polymerase II holoenzyme. Ask10p is required for Srb11p destruction in response to oxidative stress but not heat shock. Moreover, this destruction is important since the hypersensitivity of an ask10 mutant strain to oxidative stress is rescued by deleting SKB11. We further show that Ask10p is phosphorylated in response to oxidative stress but not heat shock. This modification requires the redundant mitogen-activated protein (MAP) kinase kinase Mkk1/2 but not their! normal MAP kinase target Slt2p. Moreover, the other vegetative MAP kinases-Hog1p, Fus3p, or Kss1p-are not required for Ask10p phosphorylation, suggesting the existence of an alternative pathway for transducing the Pkc1p-Bck1-->Mkk1/2 oxidative stress signal. In conclusion, Ask10p is a new component of the RNA polymerase II holoenzyme and an important regulator of the oxidative stress response. In addition, these results define a new role for the Pkc1p MAP kinase cascade (except the MAP kinase itself) in transducing the oxidative damage signal directly to the RNA polymerase II holoenzyme, thereby bypassing the stress-activated transcription factors.
English Article KeyWords Plus: RNA-POLYMERASE-II; PROTEIN-KINASE-C; BACTERIAL SIGNALING PROTEINS; MEIOTIC GENE-EXPRESSION; MAP KINASE; TRANSCRIPTION FACTOR; CELL-CYCLE; TRANSDUCTION PATHWAY; RESPONSE REGULATORS; PHOSPHOLIPASE-C Strich, R; *Fox* *Chase* Canc Ctr, Program Cell & Dev Biol, 7701 Burholme Ave, Philadelphia, PA 19111 USA. Research Addresses: *Fox* *Chase* Canc Ctr, Program Cell & Dev Biol, Philadelphia, PA 19111 USA. Duke Univ, Med Ctr, Dept Mol Biol, Durham, NC 27710 USA. Cited References: BOWDISH KS, 1994, MOL CELL BIOL, V14, P7909 BREWSTER JL, 1993, SCIENCE, V259, P1760 BROWN JL, 1993, J BACTERIOL, V175, P6908 BROWN JL, 1994, EMBO J, V13, P5186 BURCHETT SA, 2001, J BIOL CHEM, V276, P26472 COOPER JE, 1999, KEIO UNIV SYMP LIFE, V3, P11 COOPER KF, 1997, EMBO J, V16, P4665 COOPER KF, 1999, MOL CELL BIOL, V19, P3338 COURCHESNE WE, 1989, CELL, V58, P1107 CRAIG EA, 1993, MOL CELL BIOL YEAST, V2, P501 DAVENPORT KR, 1995, J BIOL CHEM, V270, P30157 DODOU E, 1997, MOL CELL BIOL, V17, P1848 ELION EA, 1990, CELL, V60, P649 FLICK JS, 1993, MOL CELL BIOL, V13, P5861 GARRINGTON TP, 1999, CURR OPIN CELL BIOL, V11, P211 GORNER W, 1998, GENE DEV, V12, P586 GREENBLATT J, 1997, CURR OPIN CELL BIOL, V9, P310 GUSTIN MC, 1998, MICROBIOL MOL BIOL R, V62, P1264 GYURIS J, 1993, CELL, V75, P791 HENGARTNER CJ, 1998, MOL CELL, V2, P43 HOLSTEGE FCP, 1998, CELL, V95, P717 IRIE K, 1993, MOL CELL BIOL, V13, P3076 JAARO H, 1997, P NATL ACAD SCI USA, V94, P3742 JUNG US, 2002, MOL MICROBIOL, V46, P781 KAMADA Y, 1995, GENE DEV, V9, P1559 KOFOID EC, 1988, P NATL ACAD SCI USA, V85, P4981 KREMS B, 1996, CURR GENET, V29, P327 KUCHIN S, 2000, P NATL ACAD SCI USA, V97, P7916 LEE KS, 1993, MOL CELL BIOL, V13, P3067 LEE J, 1999, J BIOL CHEM, V274, P16040 LEE JM, 1991, GENE EXPRESSION, V1, P149 LEVIN DE, 1990, CELL, V62, P213 1535-9778