The 19 S proteasomal subunit POH1 contributes to the regulation of c-Jun ubiquitination, stability, and subcellular localization.
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.
Institute of Parasitology, Macdonald Campus, McGill University, Ste. Anne de Bellevue, Quebec H9X 3V9, Canada.
Joseph F
JF
Nabhan
Paula
P
Ribeiro
D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D017930:Genes, Reporter; D006801:Humans; D047468:Immunoprecipitation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
D017931:DNA Primers; C109285:PSMD14 protein, human; D016755:Proto-Oncogene Proteins c-jun; D015534:Trans-Activators; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex