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 particular cancer cell lines in-vitro such as Hela, Saos-2, and MCF-7 while low to null levels were detectable in normal body tissues except for Testis [1].  This particular isoform has been identified to interact with predominantly nuclear proteins B23 [2], known to be involved in multi-faceted cellular processes such as cell division, apoptosis, ribosome biogenesis, and rRNA processing [3], as well with hnRNP-L [4], known to be involved with RNA metabolism and rRNA processing [5-6].  A previous preliminary investigation of NSP 5a3a as a potential target in Head and Neck Carcinoma revealed a novel p73 mechanism through which NSP 5a3a induced apoptosis in Head and Neck cell lines when over-expressed in-vitro.  The mechanism seemed to indicate the involvement of an unknown high molecular weight p73 isoform (140 kDA), though was independent of p53, p14, B23, and Caspase-3 [7].  Our present investigation further identified a plausible scenario, through which the involvement of TRAF2, TRADD, and DAXX along with previously unseen lower molecular weight p73 isoforms (55 and 45 kDA) induce apoptosis in Head and Neck carcinoma.  Interestingly, this novel mechanism seems to be independent of the canonical caspases involved in the intrinsic apoptotic pathway via the mitochondria as well as those participating in the death receptor pathway thru TRAF2 and TRADD.