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

Luca D'Agostino; Antonio Giordano

doi:10.18632/oncotarget.306

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

Oncotarget. 2011 Dec;2(12):1055-74. doi: 10.18632/oncotarget.306.

Authors

Luca D'Agostino¹, Antonio Giordano

Affiliation

¹ Sbarro Institute for Cancer Research and Molecular Medicine and Department of Biology, College of Science and Technology Temple University, 1900 North 12th street room 431, Philadelphia PA 19122, USA. lucadag@temple.edu

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

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / metabolism*
Apoptosis*
Carcinoma, Squamous Cell / metabolism*
Cell Cycle Proteins
Cell Division
Cell Line, Tumor
Co-Repressor Proteins
Cytoskeletal Proteins
DNA-Binding Proteins / metabolism
Head and Neck Neoplasms / metabolism*
Humans
Molecular Chaperones
Nuclear Proteins / metabolism*
Nucleophosmin
Signal Transduction
Squamous Cell Carcinoma of Head and Neck
TNF Receptor-Associated Death Domain Protein / metabolism*
TNF Receptor-Associated Factor 2 / metabolism
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / metabolism
Tumor Protein p73
Tumor Suppressor Proteins / metabolism

Substances

Adaptor Proteins, Signal Transducing
Cell Cycle Proteins
Co-Repressor Proteins
Cytoskeletal Proteins
DAXX protein, human
DNA-Binding Proteins
Molecular Chaperones
Nuclear Proteins
SPECC1 protein, human
TNF Receptor-Associated Death Domain Protein
TNF Receptor-Associated Factor 2
TP73 protein, human
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Tumor Protein p73
Tumor Suppressor Proteins
Nucleophosmin