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Sci. STKE, 25 October 2005
Vol. 2005, Issue 307, p. tw379
[DOI: 10.1126/stke.3072005tw379]


POSTTRANSLATIONAL MODIFICATIONS Phosphorylation and Isomerization

Activation of the mitogen-activated protein kinase (MAPK) cascade stimulates the activity and increases the abundance of the transcription factor AP-1, which is composed of two subunits, Jun and Fos. Monje et al. used transfected cell lines to show that the prolyl isomerase Pin1 enhanced AP-1-mediated reporter gene expression in response to growth factors. In cells overexpressing c-Jun or c-Fos, forced expression of Pin1 increased the growth factor-stimulated transcription activation of the reporter gene. Further analysis of the c-Fos and Pin1 relationship in vitro demonstrated that the interaction between Pin1 and the transactivation domain of c-Fos required phosphorylation of c-Fos by extracellular signal-regulated kinase (ERK). The interaction between c-Fos and Pin1 was also observed by coimmunoprecipitation from cells overexpressing the proteins and in glutathione-S-transferase (GST) pull-down experiments with GST-Pin1. Nonphosphorylatable mutants of c-Fos did not interact with Pin1. Thus, Pin1 appears to contribute to activation of AP-1 through interactions with both subunits--this interaction with c-Fos and an interaction with c-Jun, which had been reported previously.

P. Monje, J. Hernández-Losa, R. J. Lyons, M. D. Castellone, J. Silvio Gutkind, Regulation of the transcriptional activity of c-Fos by ERK: A novel role for the prolyl isomerase Pin1. J. Biol. Chem. 280, 35081-35084 (2005). [Abstract] [Full Text]

Citation: Phosphorylation and Isomerization. Sci. STKE 2005, tw379 (2005).

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