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Published on: June 29, 2016
Prostate-specific membrane antigen and its truncated form PSM'
Petra Mlcochová1, Cyril Barinka, Jan Tykvart
1Gilead Sciences and IOCB Research Centre, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
The Prostate
|December 25, 2008
Summary
Prostate specific membrane antigen (PSMA) variant PSM' is found in the cytosol and is proteolytically active. Data suggest PSM' arises from PSMA cleavage, not alternative splicing, impacting prostate cancer research.
Area of Science:
- Molecular Biology
- Cancer Research
- Biochemistry
Background:
- Prostate specific membrane antigen (PSMA) is overexpressed in prostate cancer and tumor neovasculature.
- PSMA splice variants exist, with PSM' prevalent in healthy prostate.
- The PSMA/PSM' mRNA ratio correlates with prostate cancer progression.
Purpose of the Study:
- Investigate the origin and localization of PSMA/PSM' variants.
- Clarify the mechanism of PSM' protein generation.
- Understand PSM' protein function and trafficking.
Main Methods:
- Differential ultracentrifugation and cell surface biotinylation.
- Western blotting and enzyme activity assays.
- N-glycosylation analysis and site-directed mutagenesis.
Main Results:
- PSM' protein expressed in LNCaP and HEK293 cells.
- PSM' localized to the cytosol and showed proteolytic activity.
- PSM' is N-glycosylated and trafficked beyond the cis-Golgi.
Conclusions:
- PSM' protein is likely generated by endoproteolytic cleavage of full-length PSMA.
- Alternative splicing is not the probable mechanism for PSM' generation.
- Findings offer new insights into PSMA biology and prostate cancer.
