Figure 6

Active p21/cyclin D2/cdk4 complexes in HTLV-1 infected cells allow for the increased phosphorylation of Rb and faster progression into the S phase. (A) Relative activity associated with cdk alone, cdk complexed with cyclin D2, and the cyclin D2/cdk/p21 complex, in both HTLV-1 infected and uninfected cells. (B) Diagram of the mechanism in which HTLV-1 alters the cell cycle in order to cause transformation. Tax transactivates both p21/waf1 and cyclin D2, which form a ternary complex with cdk4. This complex functions to phosphorylate Rb as well as to sequester p21/waf1 away from cyclin E/cdk2 complexes. Cyclin E/cdk2 complexes are thus free to further phosphorylate Rb and other cdk2 substrates. The net effect is the increased phosphorylation of Rb and other cdk substrates allowing the cell to enter the S phase more rapidly.