Abstract
Control of gene expression by stress-activated protein kinase (SAPK) cascades is crucial for combating cytotoxic stress. Elements of these cascades have been investigated in detail, but regulation of stress signal transduction from the cytoplasm to the nucleus is poorly understood. Herein are reported subcellular localization studies of fission yeast Spc1, a homolog of human p38 and budding yeast Hog1p SAPKs. Stress induces transient nuclear localization of Spc1. Nuclear translocation of Spc1 is coupled with disassociation from its activator kinase Wis1. However, Spc1 does not concentrate in the nucleus of Deltawis1 cells; therefore Wis1 does not tether Spc1 in the cytoplasm. Unphosphorylatable forms of Spc1 are dispersed in the cytoplasm and nucleus, even in cells that also produce wild-type Spc1. Thus, Spc1 must be phosphorylated by Wis1 to localize in the nucleus. Nuclear retention of Spc1 requires Atf1, a transcription factor that is the key nuclear substrate of Spc1. Nuclear localization of Atf1 requires Pcr1, a heterodimerization partner of Atf1. These studies show that phosphorylation and association with Atf1 are required for nuclear localization of Spc1.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Activating Transcription Factor 1
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Activating Transcription Factors
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Biological Transport
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cell Nucleus / metabolism
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Cytoplasm / metabolism
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DNA-Binding Proteins / physiology
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Dimerization
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Enzyme Activation
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Fungal Proteins / genetics
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Fungal Proteins / physiology*
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Gene Expression Regulation, Fungal*
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Genes, myc
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Heat-Shock Proteins / metabolism*
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Mitogen-Activated Protein Kinase Kinases*
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Mitogen-Activated Protein Kinases*
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Oxidative Stress
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Phosphorylation
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Protein Processing, Post-Translational*
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Protein Serine-Threonine Kinases / physiology*
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Recombinant Fusion Proteins / physiology
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Schizosaccharomyces / genetics*
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Schizosaccharomyces pombe Proteins*
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Transcription Factors / physiology*
Substances
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Activating Transcription Factor 1
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Activating Transcription Factors
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DNA-Binding Proteins
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Fungal Proteins
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Heat-Shock Proteins
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Pcr1 protein, S pombe
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Recombinant Fusion Proteins
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Schizosaccharomyces pombe Proteins
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Transcription Factors
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Protein Serine-Threonine Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinases
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sty1 protein, S pombe
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Mitogen-Activated Protein Kinase Kinases
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wis1 protein, S pombe