CDK9: from basal transcription to cancer and AIDS

Abstract

Cdk9 is a member of the Cdc2-like family of kinases. Its cyclin partners are members of the family of cyclin T (T1, T2a and T2b) and cyclin K. The Cdk9/cyclin T complexes appear to be involved in regulating several physiological processes. Cdk9/cyclin T1 belongs to the P-TEFb complex, and is responsible for the phosphorylation of the carboxyl-terminal domain (CTD) of the RNA Polymerase II, thus promoting general elongation. Cdk9 has also been described as the kinase of the TAK complex, which is homologous to the P-TEFb complex and involved in HIV replication. Cdk9 also appears to be involved in the differentiation program of several cell types, such as muscle cells, monocytes and neurons, suggesting that it may have a function in controlling specific differentiative pathways. In addition, Cdk9 seems to have an anti-apoptotic function in monocytes, that may be related to its control over differentiation of monocytes. This data suggests the involvement of Cdk9 in several physiological processes in the cell, the deregulation of which may be related to the genesis of transforming events, that may in turn lead to the onset of cancer. In addition, since the complex Cdk9/cyclin T1 is able to bind to the HIV-1 product Tat, the study of the functions of Cdk9/cyclin T may be of interest in understanding the basal mechanisms that regulate HIV replication.