Elucidation of Nucleophosmin Translational Regulation
Date of Award
Doctor of Philosophy (PhD)
Nucleophosmin (NPM/B23) is a highly abundant and multifunctional nucleolar oncoprotein. As a positive regulator of cellular growth and proliferation rates, NPM is overexpressed in a plethora of human cancers. NPM expression is responsive to hyperactive mammalian target of rapamycin (mTOR) signals at the level of translation, but the mechanism of this regulation is not understood. We hypothesized that the untranslated regions (UTRs) mediate translational control of the NPM mRNA by interacting with regulatory RNA-binding proteins that promote or repress translation of the transcript.
Here, I identified far upstream element (FUSE)-binding protein 1 (FBP1) as a novel regulatory mRNA-binding protein that interacts specifically with the NPM 3’ UTR to repress translation upon inhibition of mTOR. Overexpression of FBP1 resulted in translational repression of NPM mRNAs, while depletion of FBP1 caused a dramatic increase in NPM translation and resulted in enhanced overall cell proliferation. Thus, we propose that FBP1 is a key regulator of cell growth and proliferation through its ability to selectively bind the NPM 3’ UTR and repress NPM translation.
Chair and Committee
Jeffrey Arbeit, Ron Bose, David Piwnica-Worms, Reid Townsend, Katherine Weilbaecher
Olanich, Mary Elizabeth, "Elucidation of Nucleophosmin Translational Regulation" (2010). Arts & Sciences Electronic Theses and Dissertations. 104.