Role of the cyclin-dependent kinase 9-related pathway in mammalian gene expression and human diseases.
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.
Romano
Gaetano
G
Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA.
Giordano
Antonio
A
D000818:Animals; D042863:Cyclin-Dependent Kinase 9 / Q000378:metabolism*; D004194:Disease / Q000235:genetics*; D005786:Gene Expression Regulation; D006678:HIV / Q000502:physiology; D006801:Humans; D008322:Mammals / Q000235:genetics*; D014779:Virus Replication
D042863:Cyclin-Dependent Kinase 9