A novel dual signaling axis for NSP 5a3a induced apoptosis in head and neck carcinoma

Abstract

NSP 5a3a is a novel structural protein found to be over-expressed in certain cancer cell lines in-vitro such as Hela, Saos-2, and MCF-7 while barely detectable levels in normal body tissues except for Testis. This particular isoform has been known to interact with cyto- nuclear proteins B23, known to be involved in multi-faceted cellular processes such as cell division, apoptosis, ribosome biogenesis, and rRNA processing, as well as with hnRNP-L, known to be involved with RNA metabolism and rRNA processing. A previous preliminary investigation of NSP 5a3a as a potential target in Head and Neck Carcinoma revealed a novel p73 dependent mechanism through which NSP 5a3a induced apoptosis in Head and Neck cell lines when overexpressed in-vitro. Our present investigation further elucidated a novel dual axis signaling point by which NSP 5a3a induces apoptosis in Head and Neck cell line HN30 through p73-DAXX and TRAF2-TRADD. Interestingly, this novel mechanism appears independent of canonical caspases involved in the intrinsic mitochondrial pathway as well as those in the death receptor pathway thru TRAF2 and TRADD. © D'Agostino et al.