Date of Award
7-31-2006
Degree Type
Closed Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biology
First Advisor
Zhi-Ren Liu - Chair
Second Advisor
Phang C. Tai
Third Advisor
Vincent Rehder
Fourth Advisor
Jenny J. Yang
Abstract
Activities of the DEAD box (Asp-Glu-Ala-Asp) family of proteins- including RNA-dependent ATPase and RNA helicase- function in all organisms to sculpt RNA-RNA duplex and RNA-protein complexes, ensuring that necessary rearrangements are rapidly and properly resolved during genetic information processing. Identified as a prototypic member of the DEAD box family and documented as an ATPase and RNA helicase, p68 plays essential and diverse functions in the control of gene expression ranging from pre-mRNA/rRNA processing and mRNA decay/stability to transcriptional activation and initiation. Despite the early implied roles in organ maturation and tumor progression, the functional contributions of p68 to growth/differentiation regulation and cancer development remain undefined. Here, we show c-Abl-dependent phosphorylation of p68 markedly associates with abnormal cell growth and cancer development. Importantly, we characterize an unanticipated signaling module through which p68 functionally contributes to Epithelial-Mesenchymal Transition (EMT) and cell proliferation. p68, which appears to be phosphorylated by c-Abl at tyrosine 593, consequently promotes an EMT through its ability to recruit â-catenin into cell nucleus via a canonic Wnt/â-catenin axis independent way; accordingly, phosphor-p68 (phosphorylated at tyrosine 593 residue) also stimulates tumor cell growth, which requires the ATPase activity of the protein. These findings define a potential mechanism whereby phosphor-p68 recruits â-catenin into cell nucleus in ATP hydrolysis driven fashion and cooperatively regulates transcriptional programs that control an EMT. The dissertation thus demonstrates a tight coordination between DEAD box RNA helicase and cancer development.
DOI
https://doi.org/10.57709/1063843
Recommended Citation
Yang, Liuqing, "A Novel Function of DEAD Box p68 RNA Helicase In Tumor Cell Proliferation And Epithelial-Mesenchymal Transition." Dissertation, Georgia State University, 2006.
doi: https://doi.org/10.57709/1063843