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This article has been withdrawn by Paul A. Townsend, Richard A. Knight, Sean P. Barry, David S. Latchman, and Anastasis Stephanou.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