Regulation of N-myristoyltransferase by novel inhibitor proteins.
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 NIP71, which is a potential inhibitor of NMT, is homologous to heat-shock cognate 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.
Shrivastav
Anuraag
A
Department of Pathology, College of Medicine, University of Saskatchewan and Health Research Division, Saskatchewan Cancer Agency, 20 Campus Drive, Saskatoon, Saskatchewan, S7N 4H4, Canada.
Selvakumar
Ponniah
P
Bajaj
Gagan
G
Lu
Yanjie
Y
Dimmock
Jonathan R
JR
Sharma
Rajendra K
RK
D000217:Acyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D015179:Colorectal Neoplasms / Q000201:enzymology*; D005706:Gallbladder Neoplasms / Q000201:enzymology*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*
C492718:N-myristoyltransferase inhibitor protein 71, human; D009363:Neoplasm Proteins; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase