The Lats2 tumor suppressor augments p53-mediated apoptosis by promoting the nuclear proapoptotic function of ASPP1
- Yael Aylon1,
- Yaara Ofir-Rosenfeld2,
- Norikazu Yabuta3,
- Eleonora Lapi4,
- Hiroshi Nojima3,
- Xin Lu4 and
- Moshe Oren1,5
- 1Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel;
- 2Hutchison/MRC Research Centre, Cambridge CB2, United Kingdom;
- 3Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan;
- 4Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, United Kingdom
Abstract
Apoptosis is an important mechanism to eliminate potentially tumorigenic cells. The tumor suppressor p53 plays a pivotal role in this process. Many tumors harbor mutant p53, but others evade its tumor-suppressive effects by altering the expression of proteins that regulate the p53 pathway. ASPP1 (apoptosis-stimulating protein of p53-1) is a key mediator of the nuclear p53 apoptotic response. Under basal conditions, ASPP1 is cytoplasmic. We report that, in response to oncogenic stress, the tumor suppressor Lats2 (large tumor suppressor 2) phosphorylates ASPP1 and drives its translocation into the nucleus. Together, Lats2 and ASPP1 shunt p53 to proapoptotic promoters and promote the death of polyploid cells. These effects are overridden by the Yap1 (Yes-associated protein 1) oncoprotein, which disrupts Lats2–ASPP1 binding and antagonizes the tumor-suppressing function of the Lats2/ASPP1/p53 axis.
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Footnotes
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↵5 Corresponding author.
E-MAIL moshe.oren{at}weizmann.ac.il; FAX 972-8-9346004.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1954410.
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Supplemental material is available at http://www.genesdev.org.
- Received June 1, 2010.
- Accepted September 9, 2010.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press