The goal of this project is to understand the role of alteredprotein N-myristoylation as a result of 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) exposure. Hepatocellular carcinoma is the thirdleading cause of cancer death in the world. Themechanisms by which TCDD and relatedhalogenated aromatic hydrocarbons induce non-genotoxic hepatocarcinogenesis are largely unknown, and these compounds still represent an area of health risk in both the environment and workplace. Protein N-myristoylation has been implicated in the early stages of tumorigenesis, and wehypothesize that the observed TCDD-induced transcriptional modulation of specific N-myristoyltransferase (NMT) isozymes results in increased N-myristoylation ofa subset of proteins that may be involved in hepatocellular carcinogenesis. Themajor objectives of this project are to identify and characterize these proteins both in vivo and in vitro and to characterize the NMT isozymes that are transcriptionally regulated by TCDD. 2D electrophoresis, mass spectrometry, immunochemistry and fluorescence techniques will be used to identify and characterize target N-myristoylated proteins. Immunochemical, fluorescensce and in vitro enyzmatic assays willbe used to characterize NMTisozymes in terms of substrate specificity and cellular context in relation to target proteins. Thedata willprovide evidence ofpotential physiological alterations that maylead to disease states such as liver cancer
| Lyons, Gretchen E; Moore, Tamson; Brasic, Natasha et al. (2006) Influence of human CD8 on antigen recognition by T-cell receptor-transduced cells. Cancer Res 66:11455-61 |
