Date of Award
Doctor of Philosophy (PhD)
Zhi-Ren Liu - Chair
P68 is a prototypical member of the DEAD box RNA helicase family. Implicated in numerous functions such as cell proliferation, cancer metastasis, transcription regulation and pre-mRNA spllicing, p68 is a multifunctional protein whose roles are still not completely understood. In the studies presented, we found that p68 was an important regulator of numerous cancer related genes. This study focuses on the cancer related genes Snail and hTERT. We show that p68 binds to the promoter and a downstream region within each gene, suggesting that p68 operates via the same mechanism with both genes. We also show that tyrosine phosphorylated p68 is the major player in transcription regulation. p68 was also discovered to recruit CREB-binding protein to the promoters of these genes as well as aid in the removal of HDAC1 from the promoters; these findings are consistent with chromatin remodeling and active transcription. Also, we found that p68 phosphorylation level correlates with the expression level of these genes. Finally, we describe other genes that are potentially regulated by p68 in the same manner, through the use of ChiP-on-chip technology.
Carter, Christie, "The RNA Helicase p68 Regulates Transcription by Facilitating Chromatin Remodeling." Dissertation, Georgia State University, 2009.