A Schistosoma mansoni Pad1 homologue stabilizes c-Jun.
We report the cloning and functional analysis of a Pad1 homologue (SmPOH) from Schistosoma mansoni. SmPOH encodes a protein of approximately 35 kDa with high amino acid identities to yeast Pad1 (65%) and its human homologue, POH1 (78%). Members of the Pad1 family are subunits of the 26S proteasome and have been implicated as positive modulators of transcription in yeast. Recombinant SmPOH expressed in COS7 cells exhibited a punctate pattern of distribution throughout the cytoplasm and nucleus, predominantly in the nuclear periphery, a distribution consistent with that of the cellular proteasome. Transient overexpression of SmPOH in COS7 cells caused a dose-dependent stimulation in AP-1 transcriptional activity, as determined by a reporter gene assay. This effect was associated with a pronounced increase in the levels of cellular c-Jun. In vitro degradation assays further demonstrated that SmPOH specifically decreased the rate of c-Jun degradation in a dose dependent manner. Taken together, these results suggest that SmPOH, and possibly other related Pad1 proteins, function as positive modulators of transcription by increasing the stability of cellular c-Jun, making elevated amounts of this protein available for transactivation of AP-1-responsive genes.
Nabhan
Joseph F
JF
Institute of Parasitology, McGill University, Ste. Anne de Bellevue, Québec, Canada.
Hamdan
Fadi F
FF
Ribeiro
Paula
P
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D029742:Caenorhabditis elegans Proteins; D003001:Cloning, Molecular; D018432:Drug Resistance, Multiple; D005786:Gene Expression Regulation; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010802:Phylogeny; D046988:Proteasome Endopeptidase Complex; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D008565:Membrane Proteins; C109285:PSMD14 protein, human; C417911:Pad-1 protein, C elegans; D016755:Proto-Oncogene Proteins c-jun; C466434:SmPOH protein, Schistosoma mansoni; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D046988:Proteasome Endopeptidase Complex