Prostate-specific membrane antigen associates with anaphase-promoting complex and induces chromosomal instability.
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.
Rajasekaran
Sigrid A
SA
Nemours Center for Childhood Cancer Research, Alfred I. DuPont Hospital for Children, Rockland Center I, 1701 Rockland Road, Wilmington, DE 19803, USA.
Christiansen
Jason J
JJ
Schmid
Ingrid
I
Oshima
Eri
E
Ryazantsev
Sergey
S
Sakamoto
Kathleen
K
Weinstein
Jasminder
J
Rao
Nagesh P
NP
Rajasekaran
Ayyappan K
AK
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D018385:Centrosome / Q000187:drug effects / Q000648:ultrastructure; D043171:Chromosomal Instability / Q000187:drug effects; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D004285:Dogs; D006801:Humans; D015739:Nocodazole / Q000494:pharmacology; D017430:Prostate-Specific Antigen / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D008941:Spindle Apparatus / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D017430:Prostate-Specific Antigen; D015739:Nocodazole