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

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 gamma-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.