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

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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Aylon Y,Ofir-Rosenfeld Y,Yabuta N,Lapi E,Nojima H,Lu X,Oren M

doi

10.1101/gad.1954410

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

2420-9

issue

21

eissn

0890-9369

issn

1549-5477

pii

24/21/2420

journal_volume

24

pub_type

杂志文章

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