| Autor: |
Nishiwaki, Eiji, Turner, Saralinda L., Harju, Susanna, Miyazaki, Shiro, Kashiwagi, Masahide, Koh, James, Serizawa, Hiroaki |
| Zdroj: |
Molecular and Cellular Biology; October 2000, Vol. 20 Issue: 20 p7726-7734, 9p |
| Abstrakt: |
ABSTRACTThe eukaryotic cell cycle is regulated by cyclin-dependent kinases (CDKs). CDK4 and CDK6, which are activated by D-type cyclins during the G1phase of the cell cycle, are thought to be responsible for phosphorylation of the retinoblastoma gene product (pRb). The tumor suppressor p16INK4Ainhibits phosphorylation of pRb by CDK4 and CDK6 and can thereby block cell cycle progression at the G1/S boundary. Phosphorylation of the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II by general transcription factor TFIIH is believed to be an important regulatory event in transcription. TFIIH contains a CDK7 kinase subunit and phosphorylates the CTD. We have previously shown that p16INK4Ainhibits phosphorylation of the CTD by TFIIH. Here we report that the ability of p16INK4Ato inhibit CDK7-CTD kinase contributes to the capacity to induce cell cycle arrest. These results suggest that p16INK4Amay regulate cell cycle progression by inhibiting not only CDK4-pRb kinase activity but also by modulating CDK7-CTD kinase activity. Regulation of CDK7-CTD kinase activity by p16INK4Athus may represent an alternative pathway for controlling cell cycle progression. |
| Databáze: |
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