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J. Biol. Chem., Vol. 281, Issue 23, 16099-16107, June 9, 2006
The 19 S Proteasomal Subunit POH1 Contributes to the Regulation of c-Jun Ubiquitination, Stability, and Subcellular Localization*From the Institute of Parasitology, Macdonald Campus, McGill University, Ste. Anne de Bellevue, Quebec H9X 3V9, Canada The AP1 (activator protein 1) transcription factor, c-Jun, is an important regulator of cell proliferation, differentiation, survival, and death. Its activity is regulated both at the level of transcription and post-translationally through phosphorylation, sumoylation, and targeted degradation. The degradation of c-Jun by the ubiquitin proteasome pathway has been well established. Here, we report that POH1, a subunit of the 19 S proteasome lid with a recently described deubiquitinase activity, is a regulator of c-Jun. Ectopic expression of POH1 in HEK293 cells decreased the level of c-Jun ubiquitination, leading to significant accumulation of the protein and a corresponding increase in AP1-mediated gene expression. The stabilization also correlated with a redistribution of c-Jun in the nucleus. These effects were reduced by mutation of a cysteine residue in the Mpr1 pad1 N-terminal plus motif of POH1 (Cys-120) and appeared to be selective for c-Jun, because POH1 had no effect on other proteasomal substrates. Our results identify a novel mechanism of c-Jun regulation in mammalian cells.
Received for publication, November 9, 2005 , and in revised form, March 1, 2006. * This work was supported by the National Science and Engineering Research Council of Canada. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 To whom correspondence should be addressed: Institute of Parasitology, McGill University, 21111 Lakeshore Rd., MacDonald Campus, Ste. Anne de Bellevue, Quebec H9X 3V9, Canada. Tel.: 514-398-7607; Fax: 514-398-7857; E-mail: paula.ribeiro{at}mcgill.ca.
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