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The Lats2 tumor suppressor augments p53-mediated apoptosis by promoting the nuclear proapoptotic function of ASPP1

Title: The Lats2 tumor suppressor augments p53-mediated apoptosis by promoting the nuclear proapoptotic function of ASPP1
Authors: Aylon, Yael; Ofir-Rosenfeld, Yaara; Yabuta, Norikazu; Lapi, Eleonora; Nojima, Hiroshi; Lu, Xin; Oren, Moshe
Publisher Information: Cold Spring Harbor Laboratory Press
Publication Year: 2010
Collection: HighWire Press (Stanford University)
Subject Terms: Research Papers
Description: 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.
Document Type: text
File Description: text/html
Language: English
Relation: http://genesdev.cshlp.org/cgi/content/short/24/21/2420; http://dx.doi.org/10.1101/gad.1954410
DOI: 10.1101/gad.1954410
Availability: http://genesdev.cshlp.org/cgi/content/short/24/21/2420; https://doi.org/10.1101/gad.1954410
Rights: Copyright (C) 2010, Cold Spring Harbor Laboratory Press
Accession Number: edsbas.65177BA6
Database: BASE