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Title

Elucidation of Nucleophosmin Translational Regulation

Date of Award

Spring 8-15-2010

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Molecular Cell Biology)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

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.

Language

English (en)

Chair and Committee

Jason Weber

Committee Members

Jeffrey Arbeit, Ron Bose, David Piwnica-Worms, Reid Townsend, Katherine Weilbaecher

Comments

Permanent URL: https://doi.org/10.7936/K79W0CDX

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