Skip to main content
. Author manuscript; available in PMC: 2010 Feb 1.
Published in final edited form as: Cancer Res. 2009 Jan 20;69(3):810–818. doi: 10.1158/0008-5472.CAN-08-2473

Figure 6.

Figure 6

Working model for CDK6 regulation of T cell development and tumorigenesis. Activation of Notch leads to (1) activation of AKT; (2) inhibition of E2A; and (3) induction of pre-Tα transcript (one component of pre-TCR). Akt has also been shown to work downstream of pre-TCR at the β-selection checkpoint. CDK6 as a downstream mediator of Akt, can be activated by (1) Activated Akt; (2) elevated D-cyclins; (3) Increased gene expression because of reduced E2A proteins. The activated CDK6 in turn suppresses the expression of CD25, ensuring DN3 stage cells transit to DN4. Work presented here demonstrates a need for CDK6 in Notch-dependent development of thymocytes and in AKT-driven lymphomagenesis; the model postulates that CDK6 also has a role in Notch-dependent tumor formation and in mediating AKT-dependent development. Future verification of this model would provide a clear indication of links between important developmental and cell cycle pathways in thymocytes and their exploitation by tumorigenic processes.