Role of uridine kinase-like 1 (UCKL-1) in NK-mediated tumor cytotoxicity (40.9)

Abstract

NK lytic associated molecule (NKLAM), which is upregulated in NK cells by activation, has been shown to play a critical role in NK-mediated tumor cytotoxicity. We have found that NKLAM interacts with uridine kinase-like 1 protein (UCKL-1) and causes its ubiquitination and subsequent degradation. This suggests that NKLAM may play a role in tumor killing by decreasing UCKL-1 expression in target cells. In support of this is the finding that UCKL-1 mRNA is most abundant in tumor cell lines, indicating that it may be important in tumor cell growth and/or survival. In order to determine the function of UCKL-1 in tumor cell killing, K562 target cells were treated with UCKL-1 RNAi or control RNAi. Selective knockdown of UCKL-1 resulted in increased apoptosis and decreased proliferation of K562. In addition, decreased UCKL-1 expression increased the susceptibility of K562 to the apoptosis inducers staurosporine and etoposide. This finding indicates that UCKL-1 plays a role in the proliferation of K562 cells and protects them from apoptosis. By ubiquitinating and degrading UCKL-1 in target cells, NKLAM released from NK cells would therefore enhance tumor killing. This research is supported by a merit review award from the Department of Veterans Affairs.