Two Pathways of p27 Kip1 Degradation Are Required for Murine Lymphoma Driven by Myc and EBV Latent Membrane Protein 2A

Abstract

BL is a cancer that primarily affects children. The side effects of chemotherapy highlight the need for better BL treatments. Many BL tumors contain EBV, and our goal is to determine what makes EBV-positive BL different from EBV-negative BL. This may lead to more specific treatments for both types. All cases of BL require overexpression of MYC . Mice engineered to express EBV LMP2A along with MYC (LMP2A/λ- MYC mice) develop tumors much more quickly than mice only expressing MYC (λ- MYC mice). Blocking degradation of the cell cycle inhibitor protein p27 Kip1 in LMP2A/λ- MYC mice causes tumors to develop later than in λ- MYC mice, showing that p27 Kip1 degradation may play a larger role in EBV-positive BL than EBV-negative BL. Furthermore, our studies suggest the cell cycle is an attractive target as a treatment option for LMP2A-positive cancers in humans.