Investigating the Relationship Between Calorie Restriction and Mitotic Protein BubR1 in the Prevention of CIN-Induced Tumorigenesis

It is a widely known observation that aging is accompanied by decreased cellular fitness and heightened risk of acquiring diseases such as cancer. Despite this, the contributing factors that define this relationship are complex and largely undefined. Genomic and chromosomal instability in the form of aneuploidy is a hallmark of both aging and cancer, and it is theorized that the natural age-related deregulation of important mitotic processes leads to aneuploidy that increases the risk of cancer. BubR1, an important mitotic protein, functions to prevent the onset of age-related phenotypes and diseases through its mitotic functions in the spindle assembly checkpoint response and stabilization of chromosome-microtubule interactions. BubR1 protein levels decline naturally with age, which may lead to increased incidence of aneuploidy, and therefore cancer risk. Calorie restriction (CR) is a dietary intervention that is known to have both anti-aging and anti-tumorigenic effects through several well-studied pathways. Our preliminary data suggests that the protective effects of CR cannot take place in the absence of BubR1, and hence we propose that they work together to inhibit aneuploidy-induced tumorigenesis. Our data also suggests a possible mitotic role for acetylation at BubR1 lysine residue 668 (K668), which plays a significant role during interphase in regulating BubR1 stability. By unveiling a meaningful relationship between calorie restriction and BubR1, we hope to shed light on the mechanisms linking aging and disease.

Grantor dc:publisher

Creighton University

Year dc:date.issued

2022

Author dc:creator

• Bloom, Celia Rachelle

Advisor dc:contributor.advisor

• North, Brian J.

Statement dc:rights

• Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/10504/136853

OAI identifier oai:identifier

oai:cdr.creighton.edu:10504/136853