A non-enzymatic p21 protein inhibitor of stress-activated protein kinases.
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.
Shim
J
J
The Cell Biology Laboratory, Hanhyo Institutes of Technology, Kyongki-do, Korea.
Lee
H
H
Park
J
J
Kim
H
H
Choi
E J
EJ
D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014466:Ultraviolet Rays
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases