The University of Southampton
University of Southampton Institutional Repository

Retracted. ERK and the F-box protein betaTRCP target STAT1 for degradation

Retracted. ERK and the F-box protein betaTRCP target STAT1 for degradation
Retracted. ERK and the F-box protein betaTRCP target STAT1 for degradation
This article has been withdrawn by Paul A. Townsend, Richard A. Knight, Sean P. Barry, David S. Latchman, and Anastasis Stephanou. An investigation at University College London determined that a duplicated blot in Fig. 1, A and B, the GAPDH blot is the same, flipped horizontally. The withdrawing authors sincerely apologize to the scientific community for any confusion or adverse consequences resulting from the publication of the article.

Original Abstract:
The transcription factor STAT1 has roles in development, homeostasis, cellular differentiation, and apoptosis and has been postulated to function as a tumor suppressor. STAT1 is activated by tyrosine or serine phosphorylation in response to specific cytokines or following a variety of stress-induced stimuli. STAT1 activity is carefully regulated to prevent sustained STAT1-mediated transcription, although the molecular mechanisms involved in the modulation of STAT1 stability are poorly understood. Here we show that activated STAT1 is degraded at the proteasome by a mechanism involving the F-box E3 ligase, SCF(betaTRCP). Active p42/p44 MAPK-ERK phosphorylates STAT1 on serine 727 and targets it for proteasomal degradation. SCF(betaTRCP) binds wild-type STAT1 but not the nonphosphorylatable mutant STAT1(S727A). Moreover, silencing betaTRCP expression or pharmacological inhibition of ERK activity stabilized STAT1 expression. These data suggest that constitutively active ERK may inappropriately degrade STAT1, with loss of its pro-apoptotic and tumor suppressor functions.
0021-9258
16077-16083
Soond, Surinder M.
0648b6e0-c770-4e39-92da-8100fd939e0c
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Barry, Sean P.
ea289198-c2f3-4d24-9c15-93b2c439632a
Knight, Richard A.
da6172f8-cacc-4330-871a-85dea9e893a4
Latchman, David S.
71e9db7c-9075-4b49-afac-6413085378db
Stephanou, Anastasis
e9d502e8-693c-4458-a3c6-5e2844665db3
Soond, Surinder M.
0648b6e0-c770-4e39-92da-8100fd939e0c
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Barry, Sean P.
ea289198-c2f3-4d24-9c15-93b2c439632a
Knight, Richard A.
da6172f8-cacc-4330-871a-85dea9e893a4
Latchman, David S.
71e9db7c-9075-4b49-afac-6413085378db
Stephanou, Anastasis
e9d502e8-693c-4458-a3c6-5e2844665db3

Soond, Surinder M., Townsend, Paul A., Barry, Sean P., Knight, Richard A., Latchman, David S. and Stephanou, Anastasis (2008) Retracted. ERK and the F-box protein betaTRCP target STAT1 for degradation. The Journal of Biological Chemistry, 283 (23), 16077-16083. (doi:10.1074/jbc.M800384200). (PMID:18378670)

Record type: Article

Abstract

This article has been withdrawn by Paul A. Townsend, Richard A. Knight, Sean P. Barry, David S. Latchman, and Anastasis Stephanou. An investigation at University College London determined that a duplicated blot in Fig. 1, A and B, the GAPDH blot is the same, flipped horizontally. The withdrawing authors sincerely apologize to the scientific community for any confusion or adverse consequences resulting from the publication of the article.

Original Abstract:
The transcription factor STAT1 has roles in development, homeostasis, cellular differentiation, and apoptosis and has been postulated to function as a tumor suppressor. STAT1 is activated by tyrosine or serine phosphorylation in response to specific cytokines or following a variety of stress-induced stimuli. STAT1 activity is carefully regulated to prevent sustained STAT1-mediated transcription, although the molecular mechanisms involved in the modulation of STAT1 stability are poorly understood. Here we show that activated STAT1 is degraded at the proteasome by a mechanism involving the F-box E3 ligase, SCF(betaTRCP). Active p42/p44 MAPK-ERK phosphorylates STAT1 on serine 727 and targets it for proteasomal degradation. SCF(betaTRCP) binds wild-type STAT1 but not the nonphosphorylatable mutant STAT1(S727A). Moreover, silencing betaTRCP expression or pharmacological inhibition of ERK activity stabilized STAT1 expression. These data suggest that constitutively active ERK may inappropriately degrade STAT1, with loss of its pro-apoptotic and tumor suppressor functions.

This record has no associated files available for download.

More information

e-pub ahead of print date: 31 March 2008
Published date: 6 June 2008

Identifiers

Local EPrints ID: 60254
URI: http://eprints.soton.ac.uk/id/eprint/60254
ISSN: 0021-9258
PURE UUID: 4dfb21f1-40d7-4161-9069-2c63c975bbb9

Catalogue record

Date deposited: 25 Sep 2008
Last modified: 15 Mar 2024 11:19

Export record

Altmetrics

Contributors

Author: Surinder M. Soond
Author: Paul A. Townsend
Author: Sean P. Barry
Author: Richard A. Knight
Author: David S. Latchman
Author: Anastasis Stephanou

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

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×