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Review
. 2024 Nov:106-107:201-216.
doi: 10.1016/j.semcancer.2024.10.005. Epub 2024 Oct 28.

BubR1 and SIRT2: Insights into aneuploidy, aging, and cancer

Renju Pun  1 , Niti Kumari  1 , Rodaina Hazem Monieb  1 , Sachin Wagh  1 , Brian J North  2
Affiliations
Review

BubR1 and SIRT2: Insights into aneuploidy, aging, and cancer

Renju Pun et al. Semin Cancer Biol. 2024 Nov.

Abstract

Aging is a significant risk factor for cancer which is due, in part, to heightened genomic instability. Mitotic surveillance proteins such as BubR1 play a pivotal role in ensuring accurate chromosomal segregation and preventing aneuploidy. BubR1 levels have been shown to naturally decline with age and its loss is associated with various age-related pathologies. Sirtuins, a class of NAD+-dependent deacylases, are implicated in cancer and genomic instability. Among them, SIRT2 acts as an upstream regulator of BubR1, offering a critical pathway that can potentially mitigate age-related diseases, including cancer. In this review, we explore BubR1 as a key regulator of cellular processes crucial for aging-related phenotypes. We delve into the intricate mechanisms through which BubR1 influences genomic stability and cellular senescence. Moreover, we highlight the role of NAD+ and SIRT2 in modulating BubR1 expression and function, emphasizing its potential as a therapeutic target. The interaction between BubR1 and SIRT2 not only serves as a fundamental regulatory pathway in cellular homeostasis but also represents a promising avenue for developing targeted therapies against age-related diseases, particularly cancer.

Keywords: Aging; Aneuploidy; BubR1; Cancer; SIRT2; Senescence; Sirtuins.

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Conflict of interest statement

Declaration of Competing Interest The authors declare no conflict of interests

Figures

Figure 1:
Figure 1:
BubR1 expression and effect on aneuploidy and tumorigenesis.
Figure 2:
Figure 2:
Regulation of cellular and organismal phenotypes by the SIRT2/BubR1 signaling pathway. CBP, CREB-binding protein.
Figure 3:
Figure 3:
Activators and inhibitors of the SIRT2/BubR1 signaling pathway. NMN, nicotinamide mononucleotide; NAD+, nicotinamide adenine dinucleotide; Nic, nicotinamide; ADP, adenosine diphosphate.
See this image and copyright information in PMC

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