Prostate-specific membrane antigen and its truncated form PSM'
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19107881
DOI
10.1002/pros.20894
Knihovny.cz E-resources
- MeSH
- Adenocarcinoma metabolism pathology MeSH
- Cell Line MeSH
- Glycosylation MeSH
- Kidney cytology embryology metabolism MeSH
- Humans MeSH
- Lysosomes metabolism MeSH
- Microsomes metabolism MeSH
- RNA Splice Sites genetics MeSH
- Mitochondria metabolism MeSH
- Cell Line, Tumor MeSH
- Prostatic Neoplasms metabolism pathology MeSH
- Prostate-Specific Antigen chemistry genetics metabolism MeSH
- Transfection MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- RNA Splice Sites MeSH
- Prostate-Specific Antigen MeSH
BACKGROUND: Prostate specific membrane antigen (PSMA) is a type II transmembrane protein overexpressed in prostate cancer as well as in the neovasculature of several non-prostatic solid tumors. In addition to full-length PSMA, several splice variants exist in prostatic tissue. Notably, the N-terminally truncated PSMA variant, termed PSM', is prevalent in healthy prostate, and the ratio of PSMA/PSM' mRNA has been shown to correlate with cancer progression. The widely accepted hypothesis is that the PSM' protein is a translation product arising from the alternatively spliced PSM' mRNA. METHODS: Differential ultracentrifugation, cell surface biotinylation, Western blotting, and enzyme activity measurement were used to study the origin and localization of the PSMA/PSM' variants in prostatic (LNCaP; lymph-node carcinoma of the prostate) and non-prostatic (HEK293) cell lines. These experiments were further complemented by analysis of the N-glycosylation patterns of the PSMA/PSM' proteins and by site-directed mutagenesis. RESULTS: We identified PSM' protein expression in both the LNCaP cell line and a non-cancerous HEK293 human cell line transfected with a plasmid encoding full-length PSMA. Differential centrifugation revealed that PSM' is localized predominantly to the cytosol of both these cell lines and is proteolytically active. Furthermore, the PSM' protein is N-glycosylated by a mixture of high-mannose and complex type oligosaccharides and therefore trafficked beyond the cis-Golgi compartment. CONCLUSIONS: Our data suggest that the PSM' protein is likely not generated by alternative splicing of the PSMA gene but by different mechanism, probably via an endoproteolytic cleavage of the full-length PSMA.
References provided by Crossref.org
Membrane Protein Dimerization in Cell-Derived Lipid Membranes Measured by FRET with MC Simulations
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