Poly(ADP-ribose)-dependent regulation of Snail1 protein stability.

Abstract:

:Snail1 is a master regulator of the epithelial-mesenchymal transition (EMT) and has been implicated in key tumor biological processes such as invasion and metastasis. It has been previously shown that poly(ADP-ribose) polymerase-1 (PARP-1) knockdown, but not PARP inhibition, downregulates the expression of Snail1. In this study we have characterized a novel regulatory mechanism controlling Snail1 protein expression through poly(ADP-ribosyl)ation. The effect is not only limited to repression of Snail1 transcription but also to downregulated Snail1 protein stability. PARP-1 (but not PARP-2) poly(ADP) ribosylates Snail1, both in vivo and in vitro, and interacts with Snail1, an association that is sensitive to PARP inhibitors. PARP inhibition has also clear effects on EMT phenotype of different tumor cells, including Snail1 downregulation, E-cadherin upregulation, decreased cell elongation and invasiveness. Therefore, this study reveals a new regulatory mechanism of Snail1 activation through poly(ADP-ribosyl)ation with consequences in malignant transformation through EMT.

journal_name

Oncogene

journal_title

Oncogene

authors

Rodríguez MI,González-Flores A,Dantzer F,Collard J,de Herreros AG,Oliver FJ

doi

10.1038/onc.2011.153

subject

Has Abstract

pub_date

2011-10-20 00:00:00

pages

4365-72

issue

42

eissn

0950-9232

issn

1476-5594

pii

onc2011153

journal_volume

30

pub_type

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