Role of S-nitrosylation in apoptosis resistance and carcinogenesis.
Iyer AKV; Azad N; Wang LY; Rojanasakul Y
Nitric Oxide 2008 Sep; 19(2):146-151
Nitric oxide (NO) has been widely recognized as a positive regulator of tumorigenesis and cancer progression through its ability to regulate important proteins in various signal transduction pathways. S-Nitrosylation, or covalent attachment of NO to protein sulphydryl groups, has gained prominence as an important mechanism by which NO modulates physiologic and pathologic cellular responses. In this article, we discuss S-nitrosylation of two key apoptosis-regulatory proteins of the intrinsic and extrinsic death pathways, namely B-cell lymphoma-2 (Bcl-2) and FLICE-inhibitory protein (FLIP). These proteins have been shown to be upregulated in a variety of tumors and have been implicated with cancer chemoresistance through dysregulation of apoptosis, S-Nitrosylation of these proteins precludes their ubiquitination and subsequent degradation by the proteasome, thus accentuating their anti-apoptotic effect which is critical in the context of tumorigenic potential and cancer progression. We propose that such post-translational modifications of proteins by NO may be a general mechanism that tumor cells exploit to tilt the scales towards survival and proliferation by evading cell death.
Cancer; Carcinogenesis; Carcinogenicity; Carcinogens; Physiological-chemistry; Physiological-measurements; Physiological-response; Cell-alteration; Cell-biology; Cell-damage; Cell-metabolism; Cell-transformation; Chemical-binding; Chemical-reactions; Biochemical-analysis; Biochemistry
Yon Rojanasakul, Department of Pharmaceutical Sciences, West Virginia University, P.O. Box 9530, Morgantown, WV 26506
Nitric Oxide: Biology and Chemistry