Date Thesis Awarded

5-2017

Document Type

Honors Thesis

Degree Name

Bachelors of Science (BS)

Department

Biology

Advisor

Lizabeth Allison

Committee Member

Beverly Sher

Committee Member

Patty Zwollo

Committee Member

Leah Shaw

Abstract

The thyroid hormone receptor (TR) is a transcription factor that represses or activates genes whose regulatory regions bear thyroid hormone (T3) response elements (TREs). Modulation of this function requires shuttling into and out of the nucleus. This is mediated by the binding of importins and exportins to amino acid sequences within TR, called nuclear localization signals (NLSs) and nuclear export signals (NESs), respectively. The fine balance between nuclear import, retention, and export of TR has emerged as a critical control point for modulating T3-responsive gene expression, including genes that control cell proliferation, differentiation, and apoptosis. NLS-2 is a specific NLS located in the N-terminal A/B domain of TR-alpha1 and and its oncogenic form v-ErbA. NLS-2 minimally consists of the basic residue-rich motif KRKRK in TR-alpha1 of rats and humans. However, the flanking residues differ widely among vertebrates, and are likely responsible for lack of a functional NLS-2 in TR-alpha1 in some species. Yet, systemic consequences of NLS-2 flanking sequence variation remain unexplored. Further investigation of the NLS-2 variants and how these motifs synergize with protein function will enhance understanding of how even a single amino acid change can lead to TR mislocalization and potentially trigger oncogenesis.

Available for download on Sunday, May 12, 2019

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