Role of the cyclin-dependent kinase 9-related pathway in mammalian gene expression and human diseases
Gaetano Romano1, Antonio Giordano
1Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA.
Abstract:
Cyclin-dependent kinase 9 (Cdk9) is a cdc2-like serine/threonine kinase. The so-called Cdk9-related pathway comprises two Cdk9 isoforms (Cdk9-42 and Cdk9-55), cyclin T1, cyclin T2a, cyclin T2b and cyclin K. The association between Cdk9 and one of its cyclin partners forms a heterodimer, which is the main component of the positive transcription elongation factor (P-TEFb). The latter stabilizes the elongation process of RNA polymerase II (polII) transcripts. Through the control of RNA polII-mediated gene expression, the Cdk9-related pathway performs an important role in several biological processes, such as cell growth, proliferation, protection from apoptosis and differentiation. Incidentally, the P-TEFb that contains the heterodimer Cdk9-cyclin T1 is also critical for HIV-1 and HIV-2 replication in human cells. A deregulation in the Cdk9-related pathway is associated with various types of human malignancies and cardiomyocytes hypertrophy. On these grounds, the characterization of Cdk9-related pathway deregulation might have a two-fold purpose: (1) the development of novel kinase inhibitors for the treatment of cancer, AIDS and cardiac hypertrophy and (2) a better understanding of the pathogenesis and progression of these maladies.
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