ASPP1 and ASPP2 bind active RAS, potentiate RAS signalling and enhance p53 activity in cancer cells
ASPP1 and ASPP2 bind active RAS, potentiate RAS signalling and enhance p53 activity in cancer cells
RAS mutations occur frequently in human cancer and activated RAS signalling contributes to tumour development and progression. Apart from its oncogenic effects on cell growth, active RAS has tumour-suppressive functions via its ability to induce cellular senescence and apoptosis. RAS is known to induce p53-dependent cell cycle arrest, yet its effect on p53-dependent apoptosis remains unclear. We report here that apoptosis-stimulating protein of p53 (ASPP) 1 and 2, two activators of p53, preferentially bind active RAS via their N-terminal RAS-association domains (RAD). Additionally, ASPP2 colocalises with and contributes to RAS cellular membrane localisation and potentiates RAS signalling. In cancer cells, ASPP1 and ASPP2 cooperate with oncogenic RAS to enhance the transcription and apoptotic function of p53. Thus, loss of ASPP1 and ASPP2 in human cancer cells may contribute to the full transforming property of RAS oncogene.
ASPP2, ASPP1, RAS, p53, apoptosis
525-534
Wang, Y.
f5044a95-60a7-42d2-87d6-5f1f789e3a7e
Godin-Heymann, N.
28c572e1-c81b-403a-867e-f4bdcf6598be
Dan Wang, X.
ad181238-60a9-4b75-ba98-d4782f38ddb4
Bergamaschi, D.
393f1d57-af85-4410-9e17-e886a8776dd6
Llanos, S.
7444c477-9bfa-473a-ba79-5c48f06844f0
Lu, X.
8a249ba9-6273-4b53-8cf8-ffcd51be627a
April 2013
Wang, Y.
f5044a95-60a7-42d2-87d6-5f1f789e3a7e
Godin-Heymann, N.
28c572e1-c81b-403a-867e-f4bdcf6598be
Dan Wang, X.
ad181238-60a9-4b75-ba98-d4782f38ddb4
Bergamaschi, D.
393f1d57-af85-4410-9e17-e886a8776dd6
Llanos, S.
7444c477-9bfa-473a-ba79-5c48f06844f0
Lu, X.
8a249ba9-6273-4b53-8cf8-ffcd51be627a
Wang, Y., Godin-Heymann, N., Dan Wang, X., Bergamaschi, D., Llanos, S. and Lu, X.
(2013)
ASPP1 and ASPP2 bind active RAS, potentiate RAS signalling and enhance p53 activity in cancer cells.
Cell Death and Differentiation, 20 (4), .
(doi:10.1038/cdd.2013.3).
Abstract
RAS mutations occur frequently in human cancer and activated RAS signalling contributes to tumour development and progression. Apart from its oncogenic effects on cell growth, active RAS has tumour-suppressive functions via its ability to induce cellular senescence and apoptosis. RAS is known to induce p53-dependent cell cycle arrest, yet its effect on p53-dependent apoptosis remains unclear. We report here that apoptosis-stimulating protein of p53 (ASPP) 1 and 2, two activators of p53, preferentially bind active RAS via their N-terminal RAS-association domains (RAD). Additionally, ASPP2 colocalises with and contributes to RAS cellular membrane localisation and potentiates RAS signalling. In cancer cells, ASPP1 and ASPP2 cooperate with oncogenic RAS to enhance the transcription and apoptotic function of p53. Thus, loss of ASPP1 and ASPP2 in human cancer cells may contribute to the full transforming property of RAS oncogene.
Text
cdd20133a.pdf
- Version of Record
Available under License Other.
More information
Accepted/In Press date: 4 January 2013
e-pub ahead of print date: 8 February 2013
Published date: April 2013
Keywords:
ASPP2, ASPP1, RAS, p53, apoptosis
Organisations:
Centre for Biological Sciences
Identifiers
Local EPrints ID: 385900
URI: http://eprints.soton.ac.uk/id/eprint/385900
ISSN: 1350-9047
PURE UUID: efe8f490-b024-4996-ac09-519c71a8d15a
Catalogue record
Date deposited: 26 Jan 2016 09:30
Last modified: 15 Mar 2024 03:52
Export record
Altmetrics
Contributors
Author:
N. Godin-Heymann
Author:
X. Dan Wang
Author:
D. Bergamaschi
Author:
S. Llanos
Author:
X. Lu
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
