The family of
Cyclin-Dependent Kinases (CDKs) can be subdivided into two major functional groups based on their roles in cell cycle and/or transcriptional control. CDK9 is the catalytic subunit of
positive transcription elongation factor b (
P-TEFb). CDK9 is the
kinase of the TAK complex (
Tat-associated kinase complex), and binds to
Tat protein of HIV, suggesting a possible role for CDK9 in
AIDS progression. CDK9 complexed with its regulatory partner
cyclin T1, serves as a cellular mediator of the transactivation function of the
HIV Tat protein.
P-TEFb is responsible for the phosphorylation of the carboxyl-terminal domain of
RNA Pol II, resulting in stimulation of transcription. Furthermore, the complexes containing CDK9 induce the differentiation in distinct tissue. The CDK9/
cyclin T1 complex is expressed at higher level in more differentiated primary neuroectodermal and
neuroblastoma tumors, showing a correlation between the
kinase expression and
tumor differentiation grade. This may have clinical and therapeutical implications for these
tumor types. Among the CDK inhibitors two have shown to be effective against CDK9:
Roscovitine and
Flavopiridol. These two inhibitors prevented the replication of human immunodeficiency virus (HIV) type 1 by blocking Tat transactivation of the HIV type 1 promoter. These compounds inhibit CDKs by binding to the catalytic domain in place of
ATP, preventing transfer of a
phosphate group to the substrate. More sensitive therapeutic agents of CDK9 can be designed, and structural studies can add information in the understanding of this
kinase. The major features related to CDK9 inhibition will be reviewed in this article.