Authors: Shrivastav, Anuraag¹; Selvakumar, Ponniah¹; Bajaj, Gagan¹; Lu, Yanjie¹; Dimmock, Jonathan²; Sharma, Rajendra³

Source: Cell Biochemistry and Biophysics, Volume 43, Number 1, February 2005 , pp. 189-202(14)

Publisher: Humana Press

Abstract:

N-myristoylation ensures the proper function and intracellular trafficking of proteins. Many proteins involved in a wide variety of signaling, including cellular transformation and oncogenesis, are myristoylated. The myristoylation of proteins is catalyzed by the ubiquitously distributed eukaryotic enzyme N-myristoyltransferase (NMT). Previously, we reported that NMT activity is higher in colonic epithelial neoplasms than in normal-appearing colonic tissue and that the increase in NMT activity appears at an early stage in colonic carcinogenesis. Furthermore, we observed that NMT expression is elevated in colorectal and gallbladder carcinoma. In our laboratory, an endogenous NMT inhibitor protein (NIP71) was discovered from bovine brain that inhibited NMT activity in rat colonic tumors. Very recently we have demonstrated that the protein (HSC70). In addition, we have discovered that enolase is a potent inhibitor of NMT. Further work may elucidate the role of HSC70 and/or enolase in the regulation of NMT, which may lead to the development of a gene-based therapy of colorectal cancer. The interaction of oncoproteomic and oncogenomic data sets through powerful bioinformatics will yield a comprehensive database of protein properties, which will serve as an invaluable tool for cancer researchers to understand the progress of tumorigenesis.

Keywords: N-myristoyltransferase; pp60src; gallbladder carcinoma; colorectal cancer; mucosa; enolase

Document Type: Research article

DOI: http://dx.doi.org/10.1385/CBB:43:1:189

Affiliations: 1: Department of Pathology, College of Medicine, University of Saskatchewan and Health Research Division, Saskatchewan Cancer Agency, 20 Campus Drive, S7N 4H4, Saskatoon, Saskatchewan, Canada, 2: College of Pharmacy and Nutrition, University of Saskatchewan, S7N 5C9, Saskatoon, Saskatchewan, Canada, 3: Department of Pathology, College of Medicine, University of Saskatchewan and Health Research Division, Saskatchewan Cancer Agency, 20 Campus Drive, S7N 4H4, Saskatoon, Saskatchewan, Canada, Email: rsharma@scf.sk.ca

Publication date: 2005-02-01

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