PSMB9 codon 60 polymorphisms have no impact on the activity of the immunoproteasome catalytic subunit B1i expressed in multiple types of solid cancer.

ABSTRACT: The proteasome is a key regulator of cellular protein homeostasis and is a clinically validated anticancer target. The immunoproteasome, a subtype of proteasome expressed mainly in hematopoietic cells, was initially recognized for its role in antigen presentation during the immune response. Recently, the immunoproteasome has been implicated in several disease conditions including cancer and autoimmune disorders, but many of the factors contributing to these pathological processes remain unknown. In particular, the codon 60 polymorphism of the PSMB9 gene encoding the ?1i immunoproteasome catalytic subunit has been investigated in the context of a variety of diseases. Despite this, previous studies have so far reported inconsistent findings regarding the impact of this polymorphism on proteasome activity. Thus, we set out to investigate the impact of the PSMB9 codon 60 polymorphism on the expression and activity of the ?1i immunoproteasome subunit in a panel of human cancer cell lines. The ?1i-selective fluorogenic substrate Acetyl-Pro-Ala-Leu-7-amino-4-methylcoumarin was used to specifically measure ?1i catalytic activity. Our results indicate that the codon 60 Arg/His polymorphism does not significantly alter the expression and activity of ?1i among the cell lines tested. Additionally, we also examined the expression of ?1i in clinical samples from colon and pancreatic cancer patients. Our immunohistochemical analyses showed that ? 70% of clinical colon cancer samples and ? 53% of pancreatic cancer samples have detectable ?1i expression. Taken together, our results indicate that the ?1i subunit of the immunoproteasome is frequently expressed in colon and pancreatic cancers but that the codon 60 genetic variants of ?1i display similar catalytic activities and are unlikely to contribute to the significant inter-cell-line and inter-individual variabilities in the immunoproteasome activity.

SUBMITTER: Park JE 

PROVIDER: S-EPMC3767749 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature