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.
Vives
Virginie
V
Ludwig Institute for Cancer Research, University College London, London W1W 7BS, United Kingdom.
Su
Jian
J
Zhong
Shan
S
Ratnayaka
Indrika
I
Slee
Elizabeth
E
Goldin
Robert
R
Lu
Xin
X
D000483:Alleles; D000818:Animals; D005804:Genes, Lethal; D016147:Genes, Tumor Suppressor; D006238:Haploidy; D006579:Heterozygote; D008223:Lymphoma / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C511437:Trp53bp2 protein, mouse; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins