Abstract
The stress-activated protein kinases (SAPKs), which are identical to the c-Jun amino-terminal kinases (JNKs), are activated in response to a variety of cellular stresses, including DNA damage, heat shock or tumour-necrosis factor-alpha. SAPK, a subfamily of the mitogen-activated protein (MAP) kinases, is a major protein kinase that phosphorylates c-Jun and other transcription factors. SAPK phosphorylation of transcription factors is important in stress-activated signalling cascades. Here we report that the protein p21 WAF1/CIP1/Sd:1, a DNA-damage-inducible cell-cycle inhibitor, acts as an inhibitor of the SAPK group of mammalian MAP kinases. This highlights a new biochemical activity of p21, which may provide the first evidence for a non-enzymatic inhibitory protein for SAPK. We suggest that p21, by inhibiting SAPK, may participate in regulating signalling cascades that are activated by cellular stresses such as DNA damage.
MeSH terms
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Amino Acid Sequence
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Animals
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Carrier Proteins / metabolism
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Cell Line
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / metabolism*
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Glutathione Transferase / genetics
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Glutathione Transferase / metabolism
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinases*
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Molecular Sequence Data
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Phosphorylation
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Transfection
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Ultraviolet Rays
Substances
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Carrier Proteins
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Recombinant Fusion Proteins
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Glutathione Transferase
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Calcium-Calmodulin-Dependent Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinases