ASPP2 is a haploinsufficient tumor suppressor that cooperates with p53 to suppress tumor growth
ASPP2- Virginie Vives1,3,
- Jian Su1,3,
- Shan Zhong1,3,
- Indrika Ratnayaka1,
- Elizabeth Slee1,
- Robert Goldin2, and
- Xin Lu1,4
- 1 Ludwig Institute for Cancer Research, University College London, London W1W 7BS, United Kingdom;
- 2 Department of Pathology, Imperial College London, Faculty of Medicine at St. Mary’s, London W2 1PG, United Kingdom
- 3
↵3 These authors contributed equally to this work.
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.
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Footnotes
- 4
↵4 Corresponding author.
↵4 E-MAIL x.lu{at}ludwig.ucl.ac.uk; FAX 44-20-7878-4040.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.374006
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- Received November 25, 2005.
- Accepted February 27, 2006.
- Copyright © 2006, Cold Spring Harbor Laboratory Press