| Autor: |
Janice L, Walker, Paola, Castagnino, Betty M, Chung, Marcelo G, Kazanietz, Richard K, Assoian |
| Rok vydání: |
2006 |
| Předmět: |
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| Zdroj: |
The Journal of biological chemistry. 281(50) |
| ISSN: |
0021-9258 |
| Popis: |
p21(cip1) inhibits S phase entry by binding to cyclin-cdk2 (cyclin-dependent kinase-2) complexes. The levels of p21(cip1) are rapidly induced after mitogenic stimulation of quiescent fibroblasts and then down-regulate as the cells reach late G(1) phase and activate cyclin E-cdk2. In this study, we have shown that pharmacological inhibition of protein kinase C (PKC), expression of dominant negative PKCdelta, or knockdown of PKCdelta with small interfering RNA elevates p21(cip1) protein levels in mouse embryo fibroblasts. This effect is selective, post-transcriptional, and proteasome-dependent but distinct from previously identified post-transcriptional control mechanisms involving cyclin D1 and Skp2. PKCdelta inhibition results in a reduced entry into S phase, and this effect is not detected in p21(cip1)-null cells. Thus, post-transcriptional destabilization of p21(cip1) appears to be a major mitogenic effect of PKCdelta in fibroblasts. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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