title: The MAPKKKs Ste11 and Bck1 jointly transduce the high oxidative stress signal through the cell wall integrity MAP kinase pathway.
abstract: Oxidative stress stimulates the Rho1 GTPase, which in turn induces the cell wall integrity (CWI) MAP kinase cascade. CWI activation promotes stress-responsive gene expression through activation of transcription factors (Rlm1, SBF) and nuclear release and subsequent destruction of the repressor cyclin C. This study reports that, in response to high hydrogen peroxide exposure, or in the presence of constitutively active Rho1, cyclin C still translocates to the cytoplasm and is degraded in cells lacking Bck1, the MAPKKK of the CWI pathway. However, in mutants defective for both Bck1 and Ste11, the MAPKKK from the high osmolarity, pseudohyphal and mating MAPK pathways, cyclin C nuclear to cytoplasmic relocalization and destruction is prevented. Further analysis revealed that cyclin C goes from a diffuse nuclear signal to a terminal nucleolar localization in this double mutant. Live cell imaging confirmed that cyclin C transiently passes through the nucleolus prior to cytoplasmic entry in wild-type cells. Taken together with previous studies, these results indicate that under low levels of oxidative stress, Bck1 activation is sufficient to induce cyclin C translocation and degradation. However, higher stress conditions also stimulate Ste11, which reinforces the stress signal to cyclin C and other transcription factors. This model would provide a mechanism by which different stress levels can be sensed and interpreted by the cell.
authors.affiliation: Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Stratford, NJ, 08055 USA.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Stratford, NJ, 08055 USA.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Stratford, NJ, 08055 USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Willis
authors.affiliation: Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Stratford, NJ, 08055 USA.
authors.forename: Katrina F
authors.initials: KF
authors.lastname: Cooper
keywords: MAPK signal transduction pathways; cyclin C; mitochondrial morphology; oxidative stress; programmed cell death; protein degradation