Seminars Archive
CDK7 and CDK9 at the interface of Cell Cycle and Transcription Regulation: from structure to function
Laboratory of Molecular Biophysics - University of Oxford and Istituto di Ricerche di Biologia Molecolare – Pomezia – Roma
Abstract
Cyclin Dependent Kinases (CDKs) regulate the cell division cycle, apoptosis, transcription and differentiation in addition to functions in the nervous system. Their deregulation is involved in different diseases ranging from several types of cancer to AIDS. We solved the crystal structures of CDK7 and of the CDK9/CycT complex. We then used them as starting points to define mechanism of regulation and protein recognition properties for those kinases. For their role in cell cycle, specificity determinants for CDKs cross-phosphorylation were determined. Relatively to their role in transcription, mechanism of sequential action of CDK7 and CDK9 on RNA polymerase II was clarified. Finally, as therapeutic targets, drug development programs were started for both CDKs.
