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Post-translational modification of NF-kB: regulation of stability and gene expression

Hertlein, Erin K.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1167336380

Abstract Details

2006, Doctor of Philosophy, Ohio State University, Integrated Biomedical Science.
NF-kB was discovered over 20 years ago, and while the knowledge of this transcription factor has been considerably expanded, it is still not completely understood how a single signaling pathway regulates such a diverse array of events in cells. One of the ways in which this transcription factor may target a variety of genes under different conditions is through post-translational modifications that regulate how the complex binds to gene promoters, as well as how it binds to other co-factors. This thesis is designed to investigate how these modifications, specifically phosphorylation, regulate gene expression and control NF-kB mediated events. Chapter one is a general introduction to NF-kB, and also discusses some of the known NF-kB target genes as well as diseases that are known to occur at least in part due to deregulated NF-kB activity. Chapter two investigates the effect of phosphorylation on the stability of IkBb, an inhibitor of NF-kB. We show that this regulation is important for maintenance of normal cell growth in mouse embryo fibroblasts. Chapters three and four focus on a different aspect of phosphorylation. In contrast to how protein phosphorylation controls stability, these chapters are designed specifically to determine how this modification affects target gene transcription. The goal of this part of the thesis is to further elucidate whether specific phosphorylation at particular resides can differentially affect sub-sets of endogenous genes. Finally, chapter five discusses the attempts to determine the role of NF-kB post-translation modification in other cell types, as well as discuss the importance of increasing our current knowledge as to how this complicated transcription factor signals. Insight into how NF-kB differentially regulates subsets of genes may allow for development of specific therapeutic targets. Currently, drugs that inhibit NF-kB on a broad level are in use, however these types of treatments may have undesirable side effects due to non-specific inhibition of other beneficial pathways in the cell. The ability to develop more specific inhibitors that affect only a small number of genes important in a particular disease will allow for more efficient therapies.
Denis Guttridge (Advisor)
145 p.
NF-kB; post-translational modification; gene expression

Recommended Citations

Citations

  • Hertlein, E. K. (2006). Post-translational modification of NF-kB: regulation of stability and gene expression [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1167336380

    APA Style (7th edition)

  • Hertlein, Erin. Post-translational modification of NF-kB: regulation of stability and gene expression. 2006. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1167336380.

    MLA Style (8th edition)

  • Hertlein, Erin. "Post-translational modification of NF-kB: regulation of stability and gene expression." Doctoral dissertation, Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=osu1167336380

    Chicago Manual of Style (17th edition)

osu1167336380
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© 2006, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.