Open AccessRegulation of CDK7–Carboxyl-Terminal Domain Kinase Activity by the Tumor Suppressor p16INK4A Contributes to Cell Cycle Regulation
Author(s) -
Eiji Nishiwaki,
Saralinda L. Turner,
Susanna Harju,
Shiro Miyazaki,
Masahide Kashiwagi,
James Koh,
Hiroaki Serizawa
Publication year - 2000
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.20.20.7726-7734.2000
Subject(s) - cyclin dependent kinase , cyclin dependent kinase 7 , transcription factor ii h , biology , cyclin dependent kinase 6 , cyclin dependent kinase 1 , microbiology and biotechnology , cell cycle , rna polymerase ii , cyclin dependent kinase 9 , cyclin dependent kinase 4 , cyclin dependent kinase 2 , cancer research , kinase , protein kinase a , biochemistry , cell , gene expression , promoter , gene
The eukaryotic cell cycle is regulated by cyclin-dependent kinases (CDKs). CDK4 and CDK6, which are activated by D-type cyclins during the G1 phase of the cell cycle, are thought to be responsible for phosphorylation of the retinoblastoma gene product (pRb). The tumor suppressor p16INK4A inhibits 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 p16INK4A inhibits phosphorylation of the CTD by TFIIH. Here we report that the ability of p16INK4A to inhibit CDK7-CTD kinase contributes to the capacity to induce cell cycle arrest. These results suggest that p16INK4A may 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 p16INK4A thus may represent an alternative pathway for controlling cell cycle progression.