Moran Benhar, PhD
Associate Professor of Biochemistry
PhD, 2002 - The Hebrew University, Jerusalem
Redox regulation in inflammation and cancer
Reactive oxygen and nitrogen species, such as hydrogen peroxide and nitric oxide, affect various cellular processes via redox-based modifications of specific cysteines within proteins. Several cysteine modifications, such as sulfenylation and nitrosylation, are increasingly recognized to regulate a wide range of cellular processes, including cell proliferation, differentiation, and death. In our lab, we use cutting-edge proteomic and biochemical tools to explore the roles of protein redox modifications (mainly cysteine nitrosylation) in cellular communication, inflammation, and cancer.
Our main research goals are: (1) identify nitrosylated proteins in cancer cells; (2) explore how redox modifications regulate oncogenic and inflammatory pathways; (3) develop new proteomic methods to analyze protein S-nitrosylation.
Engelman R, Ziv T, Arner ES and Benhar M. 2016. Inhibitory nitrosylation of mammalian thioredoxin reductase 1: molecular characterization and evidence for its functional role in cellular nitroso-redox imbalance.
Free Radic. Biol. Med. 97:375-85.
Kronenfeld G, Engelman R, Weisman-Shomer P, Atlas D and Benhar M. 2015. Thioredoxin-mimetic peptides as catalysts of S-denitrosylation and anti-nitrosative stress agents. Free Radic. Biol. Med. 50, 138-46.
Ben-Lulu S, Ziv T, Admon A, Weisman-Shomer P and Benhar M. 2014. A substrate trapping approach identifies proteins regulated by reversible S-nitrosylation. Mol. Cell. Proteomics. 13, 2573-83.
Engelman R, Weisman-Shomer P, Ziv T, Xu J, Arner ES and Benhar M. 2013. Multilevel regulation of 2-Cys Peroxiredoxin reaction cycle by S-Nitrosylation. J. Biol. Chem. 288, 11312-24.
Overview of NO signaling through S-nitrosylation.
The free radical nitric oxide (NO) is involved in numerous cellular and organismal processes, including cell division, migration, differentiation and death. NO influences various processes through targeted modification of cysteine residues in proteins, generating S-nitrosylated proteins (protein-SNO). Nitrosylation of specific cysteine residues has been detected in well over 100 proteins of all classes and appears to be a principal mechanism by which NO signals are transduced. Much like protein phosphorylation, nitrosylation influences protein activity, protein-protein interactions and protein location. The level of nitrosylation is controlled by the opposing action of NO synthase (NOS) and denitrosylases, in particular, S-nitrosoglutathione reductase (GSNOR) and thioredoxin (Trx). Protein nitrosylation has been found to play important roles in cellular signaling and other biological processes whereas dysregulated nitrosylation may contribute to cellular dysfunction and disease.