DHHC3 Contributions to Breast Cancer
Annual rept. 1 Sep 2011-31 Aug 2012
CHILDREN'S HOSPITAL CORP BOSTON MA
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Many proteins resident in tetraspanin-enriched microdomains, key structural and functional platforms in breast cancer, are regulated by post-translational palmitoylation. Our preliminary data suggests that DHHC3, a palmitoylating enzyme, plays a critical role in breast cancer cell growth, invasion, and or metastasis. However, little is known about which proteins are palmitoylated by DHHC3 in breast cancer. Thus, we proposed to comprehensively identify DHHC3 substrates by integrating our palmitoyl protein identification and site characterization method with triplex SILAC. In year 1, we established this multiplexed quantitative palmitoyl-proteomics method in our lab. We tested and optimized the method during the analysis of cancer cells stimulated by epidermal growth factor. In this time- and membrane domain resolved proteomics experiment, we found that many translation factors are palmitoylated and targeted to membranes, while some cell adhesion molecules are depalmitoylated and dissociated from certain membrane microdomains, In response to epidermal growth factor simulation.
- Medicine and Medical Research