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
J F
JF
Institute of Parasitology, McGill University, 21,111 Lakeshore Road, Québec, H9X3V9, Ste. Anne de Bellevue, Canada.
Hamdan
F F
FF
Ribeiro
P
P
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D029742:Caenorhabditis elegans Proteins; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; C417911:Pad-1 protein, C elegans; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1