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 over-expressed 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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism*
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Apoptosis*
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Carcinoma, Squamous Cell / metabolism*
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Cell Cycle Proteins
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Cell Division
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Cell Line, Tumor
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Co-Repressor Proteins
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Cytoskeletal Proteins
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DNA-Binding Proteins / metabolism
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Head and Neck Neoplasms / metabolism*
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Humans
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Molecular Chaperones
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Nuclear Proteins / metabolism*
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Nucleophosmin
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Signal Transduction
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Squamous Cell Carcinoma of Head and Neck
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TNF Receptor-Associated Death Domain Protein / metabolism*
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TNF Receptor-Associated Factor 2 / metabolism
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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / metabolism
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Tumor Protein p73
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Tumor Suppressor Proteins / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Cell Cycle Proteins
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Co-Repressor Proteins
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Cytoskeletal Proteins
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DAXX protein, human
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DNA-Binding Proteins
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Molecular Chaperones
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Nuclear Proteins
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SPECC1 protein, human
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TNF Receptor-Associated Death Domain Protein
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TNF Receptor-Associated Factor 2
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TP73 protein, human
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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
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Tumor Protein p73
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Tumor Suppressor Proteins
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Nucleophosmin