Type of Document Dissertation Author Lin, Chunru Author's Email Address clin8@student.gsu.edu URN etd-07202006-143728 Title Functional Role of Dead-Box P68 RNA Helicase in Gene Expression Degree Ph.D. Department Biology Advisory Committee
Advisor Name Title Zhi-Ren Liu Committee Chair Chung-Dar Lu Committee Member Jenny J. Yang Committee Member Susanna F. Greer Committee Member Keywords
- p68
- phosphorylation
- EMT
- Snail
- HDAC1
- NuRD
- ATPase
- DEAD-box
- transcriptional regulation
- protein-protein interaction
Date of Defense 2006-06-21 Availability unrestricted Abstract How tumor cells migrate and metastasize from primary sites requires four major steps: invasion, intravasation, extravasation and proliferation from micrometastases to malignant tumor. The initiation of tumor cell invasion requires Epithelial-Mesenchymal Transition (EMT), by which tumor cells lose cell-cell interactions and gain the ability of migration. The gene expression profile during the EMT process has been extensively investigated to study the initiation of EMT. In our studies, we indicated that tyrosine phosphorylation of human p68 RNA helicase positively associated with the malignant status of tumor tissue or cells. Studying of this relationship revealed that p68 RNA helicase played a critical role in EMT progression by repression of E-cadherin as an epithelial marker and upregulation of Vimentin as a mesenchymal marker. Insight into the mechanism of how p68 RNA helicase represses E-cadherin expression indicated that p68 RNA helicase initiated EMT by transcriptional upregulation of Snail. Human p68 RNA helicase has been documented as an RNA-dependent ATPase. The protein is an essential factor in the pre-mRNA splicing procedure. Some examples show that p68 RNA helicase functions as a transcriptional coactivator in ATPase dependent or independent manner. Here we indicated that p68 RNA helicase unwound protein complexes to modulate protein-protein interactions by using protein-dependent ATPase activity. The phosphorylated p68 RNA helicase displaced HDAC1 from the chromatin remodeling MBD3:Mi2/NuRD complex at the Snail promoter. Thus, our data demonstrated an example of protein-dependent ATPase which modulates protein-protein interactions within the chromatin remodeling machine.Files
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