All ETDs from UAB

Advisory Committee Chair

William J Placzek

Advisory Committee Members

Louise T Chow

Anita B Hjelmeland

Chad M Petit

Tim M Townes

Document Type

Dissertation

Date of Award

2019

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Protein-protein interactions are critical for cell life. One aspect of cellular regulation where such protein-protein interactions occur is in the highly regulated process of programmed cell death (or apoptosis). Apoptosis is critical for normal tissue homeostasis, differentiation, and if dysregulated is a driver of disease including cancers. At the center of apoptotic regulation is the BCL2 protein family whose intra-familial protein-protein interactions balance cell stress signaling either allowing the cell to survive or inducing mitochondrial cell death. These BCL2 protein interactions are accomplished through the BH3 motif. While unique to the BCL2 family, a similar motif, the reverse BH3, has been identified in non-BCL2 proteins. One such protein is the cell cycle inhibitor, P18, that exhibits a reverse BH3 near its C-terminus. Here we demonstrate the ability of the anti-apoptotic BCL2 family member to interact with the rBH3 of P18 and thereby establish a novel protein-protein interaction. Further this interaction is able to mitigate P18’s inhibition of the cell cycle. In summary, we present a new protein-protein interaction that connects at the protein level both cell cycle and cell death regulation.

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