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

ASPP2
  1. Virginie Vives1,3,
  2. Jian Su1,3,
  3. Shan Zhong1,3,
  4. Indrika Ratnayaka1,
  5. Elizabeth Slee1,
  6. Robert Goldin2, and
  7. Xin Lu1,4
  1. 1 Ludwig Institute for Cancer Research, University College London, London W1W 7BS, United Kingdom;
  2. 2 Department of Pathology, Imperial College London, Faculty of Medicine at St. Mary’s, London W2 1PG, United Kingdom
  1. 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.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.374006

    • Received November 25, 2005.
    • Accepted February 27, 2006.
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