Prostate-specific membrane antigen associates with anaphase-promoting complex and induces chromosomal instability.

Abstract

Prostate-specific membrane antigen (PSMA) is a transmembrane protein highly expressed in advanced and metastatic prostate cancers. The pathologic consequence of elevated PSMA expression in not known. Here, we report that PSMA is localized to a membrane compartment in the vicinity of mitotic spindle poles and associates with the anaphase-promoting complex (APC). PSMA-expressing cells prematurely degrade cyclin B and exit mitosis due to increased APC activity and incomplete inactivation of APC by the spindle assembly checkpoint. Further, expression of PSMA in a karyotypically stable cell line induces aneuploidy. Thus, these findings provide the first evidence that PSMA has a causal role in the induction of aneuploidy and might play an etiologic role in the progression of prostate cancer.

• Authors: Sigrid A Rajasekaran, Jason J Christiansen, Ingrid Schmid, Eri Oshima, Sergey Ryazantsev, Kathleen Sakamoto, Jasminder Weinstein, Nagesh P Rao, Ayyappan K Rajasekaran
• Journal: Molecular cancer therapeutics (Mol Cancer Ther) Vol. 7 Issue 7 Pg. 2142-51 (Jul 2008) ISSN: 1535-7163 [Print] United States
• PMID: 18645024 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• CCNB1 protein, human
• Cyclin B
• Cyclin B1
• Ubiquitin-Protein Ligase Complexes
• Anaphase-Promoting Complex-Cyclosome
• Prostate-Specific Antigen
• Nocodazole

Topics

• Anaphase-Promoting Complex-Cyclosome
• Animals
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Centrosome (drug effects, ultrastructure)
• Chromosomal Instability (drug effects)
• Cyclin B (metabolism)
• Cyclin B1
• Dogs
• Humans
• Nocodazole (pharmacology)
• Prostate-Specific Antigen (metabolism, ultrastructure)
• Protein Binding (drug effects)
• Protein Transport (drug effects)
• Spindle Apparatus (metabolism)
• Ubiquitin-Protein Ligase Complexes (metabolism)