Proteomics of Nedd8 Pathway in Human Prostate Cancer
Annual rept. 15 Jul 2004-14 Jul 2005
CALIFORNIA UNIV IRVINE
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Recently proteomic analysis has discovered that Nedd8 neutral precursor cell expressed and developmentally down-regulated 8 expression level is dramatically reduced in human prostate cancer compared to benign prostatic epithelium. In addition, a number of high molecular weight Nedd8 modified proteins were observed, and one of them was markedly reduced in intensity 2-fold in the malignant tissue. The results suggest that under-expression of Nedd8 will result in forming of less number andor less amount of Nedd8 modified proteins in prostate cancer. Our hypothesis is that Nedd8 regulates the balance between cell proliferation and cell death by controlling the formation of specific cullin-containing ubiquitin ligase through neddylation and that loss of Nedd8 leads to reduced degradation of proliferative and anti-apoptotic proteins. Novel targets for neddylation in prostate tissue could identify specific mediators of prostate cancer development and progression. Therefore, the objective of this project is to study Nedd8 pathway in human prostate cancer employing mass spectrometry-based approaches to identify and characterize Nedd8 modified proteins from human prostate tissues. An additional objective is to establish a model system using benign and malignant prostatic epithelial cells for future study of the biological role of Nedd8 pathway associated with down-regulation of Nedd8 expression in prostate cancer.
- Medicine and Medical Research