ASPP2 is a haploinsufficient tumor suppressor that cooperates with p53 to suppress tumor growth

Abstract

ASPP2 stimulates the apoptotic function of the p53 family in vivo. We show here that ASPP2−/− pups died before weaning. This postnatal lethality was significantly enhanced in p53+/− background and both deletions are synthetic lethal. ASPP2+/− mice developed spontaneous tumors. The tumor onset was accelerated by γ-irradiation or in p53+/− background. Tumors derived from ASPP2+/− mice retained wild-type ASPP2 allele even though some of them lost p53. These provide the first genetic evidence that ASPP2 is a haploinsufficient tumor suppressor that shares overlapping function(s) with p53 in mouse development and tumor suppression.