A family of proteins designated cyclin dependent kinases (Cdks) are critical regulators of cell cycle progression. Cdk family members, including Cdc2 p34, Cdk1�C9, PISSLRE, KKIALRE, PITSLRE, and PCTAIRE 1�C3 are constitutively expressed throughout the cell cycle. Cdc2 p34 activity peaks during mitosis and Cdk2 activity rises in late G1 or early S phase. Cdk4 and Cdk6 are critically involved in G1 to S phase progression. The functions of Cdk3, Cdk5b, PISSLRE, KKIALRE and PCTAIRE 1�C3 are less well defined. Cdk9 (also designated PITALRE) has been shown to specifically phosphorylate the retinoblastoma protein. The more recently cloned Drosophila protein, P-TEFb, is thought to be the homolog of mammalian PITALRE. P-TEFb has been shown to be required for HIV Tat transcriptional activation.