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Evidence for a differential modulation of p53-phosphorylating kinases by the cyclin-dependent kinase inhibitor p21WAFI/C1P1
| Content Provider | Scilit |
|---|---|
| Author | Neise, Denise Sohn, Dennis Budach, Wilfried Jänicke, Reiner U. |
| Copyright Year | 2010 |
| Description | Although initially described as a regulator of cell cycle progression, the cyclin-dependent kinase inhibitor p21 is now known to also modulate various other biological processes including transcription, differentiation and apoptosis. These versatile activities of p21 are mainly mediated via direct binding to various transcription factors, pro-apoptotic proteins and kinases that are usually inhibited by this interaction. Here we provide in vitro evidence that p21 not only inhibits, but also activates certain kinases in a remarkable substrate-dependent manner. Whereas phosphorylation of the tumor suppressor p53 by several isoforms of the cJun N-terminal kinases (JNKs) was greatly attenuated in the presence of p21, phosphorylation of cJun remained either unaffected or was even enhanced. Furthermore, p21 strongly increased phosphorylation of cFos and MBP by ERK1 and ERK2, while p53 phosphorylation was increased and inhibited, respectively. Also p38α and glycogen synthase kinase-3 beta (GSK-3β) were found differentially regulated by p21 in a substrate-dependent manner, while casein kinase-1 epsilon (CK1ε) was not affected. Together with our finding that the stress-induced p53 phosphorylation pattern differs greatly between p21-proficient and -deficient HCT116 colon carcinoma cells, our results suggest that p21 is able to influence kinase activities both in a negative and positive manner. |
| Related Links | https://www.landesbioscience.com/journals/cc/NeiseCC9-17.pdf |
| Ending Page | 3583 |
| Page Count | 9 |
| Starting Page | 3575 |
| ISSN | 15384101 |
| e-ISSN | 15514005 |
| DOI | 10.4161/cc.9.17.12799 |
| Journal | Cell Cycle |
| Issue Number | 17 |
| Volume Number | 9 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2010-09-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cell Cycle Biochemistry and Molecular Biology Apoptosis Transcription Factors Cyclin Differentiation Phosphorylation P21 Inhibitor Kinase Cjun Modulate |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Developmental Biology Medicine Molecular Biology |
