The proposed relationship of MYC, LMP2A, and p27^kip1in lymphoma development. (Top) In an λ-MYC mouse model, overexpression of MYC results in repression of Cdkn1b transcription and increases p27^kip1 degradation, leading to an increase in proliferation. The remaining pool of p27^kip1 partially impedes MYC-induced cell cycle progression and downregulates MYC. Abundant expression of MYC also induces p53 pathway activation. Both p27^kip1 and p53 are able to prevent uncontrolled proliferation for a certain length of time. At a later step, selection pressure forces deregulated MYC cells to overcome the apoptosis mechanism mediated by p53, and a lymphoma develops. (Bottom) In the presence of LMP2A, p27^kip1 turnover is more rapid and weakens the MYC repression network, resulting in a high level of MYC. Although the p53 pathway is induced as a result of overexpression of MYC, cell cycle progression and proliferation outpaces the rate of apoptosis. A severely low level of p27^kip1 may relieve the selection pressure, and a lymphoma develops without the need to inactivate the p53 pathway.