The goal of this project is to understand the role of altered protein N-myristoylation as a result of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure. Hepatocellular carcinoma is the third leading cause of cancer death in the world. The mechanisms by which TCDD and related halogenated 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 we hypothesize that the observed TCDD-induced transcriptional modulation of specific N-myristoyltransferase (NMT) isozymes results in increased N-myristoylation of a subset of proteins that may be involved in hepatocellular carcinogenesis. The major 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, fluorescence and in vitro enzymatic assays will be used to characterize NMT isozymes in terms of substrate specificity and cellular context in relation to target proteins. The data will provide evidence of potential physiological alterations that may lead to disease states such as liver cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32CA111040-01A1
Application #
6940949
Study Section
Special Emphasis Panel (ZRG1-F09 (20))
Program Officer
Lohrey, Nancy
Project Start
2006-01-01
Project End
2008-12-31
Budget Start
2006-01-01
Budget End
2006-12-31
Support Year
1
Fiscal Year
2005
Total Cost
$41,796
Indirect Cost
Name
National Research Center/Environment & Health
Department
Type
DUNS #
City
Neuherberg
State
Country
Germany
Zip Code
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