Year: 2000
Type: article
Abstract: The cdk-activating kinase (CAK) activates cyclin-dependent kinases (cdks) that control cell-cycle progression by phosphorylating a threonine residue conserved in cdks. CAK from humans contains p40MO15 (cdk7), cyclin H and MAT1, which are also subunits of transcription factor IIH where they phosphorylate the C-terminal domain of the large subunit of RNA polymerase II. In contrast, budding yeast Cak1p is a monomeric enzyme without C-terminal domain kinase activity. Here, we analyze CAK activities in HeLa cells using cdk2-affinity chromatography. In addition to MO15, a second CAK activity was detected that runs on gel filtration at 30-40 kDa. This activity phosphorylated and activated cdk2 and cdk6. Furthermore, this 'small CAK' activity resembled Cak1p rather than MO15 in terms of substrate specificity, reactivity to antibodies against MO15 and Cak1p, and sensitivity to 5'-fluorosulfonylbenzoyladenosine, an irreversible inhibitory ATP analog. Our findings suggest the presence of at least two different CAK activities in human cells.
Source: European Journal of Biochemistry
Authors: Philipp Kaldis, Mark J. Solomon
Institution: Yale University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1539696293