Page 9 - GPD-3-4

Gene & Protein in Disease

REVIEW ARTICLE
Understanding the fundamental mechanisms

and conditions of the tumor-suppressive and
oncogenic roles of sirtuins in cancer: A review

1
Daniela Szabóová , Zuzana Guľašová 2 , Zdenka Hertelyová 2 , and
1
Roman Beňačka *
1 Department of Pathophysiology, Faculty of Medicine, P.J. Šafarik University, Košice, Slovakia
2 Center of Clinical and Preclinical Research MEDIPARK, P.J. Šafarik University, Košice, Slovakia

Abstract

Silent information regulators (SIRTs) or sirtuins represent a group of class III
nicotinamide adenine dinucleotide–dependent histone deacetylases. In mammals,
seven types of sirtuins are distinguished, differing in their target structures,
enzymatic activities, and subcellular localization. Histone deacetylation is a form of
epigenetic regulation of gene expression that can cause activation or deactivation of
selected genetic targets. Activation of sirtuins is part of the response to nutritional
and environmental stimuli (starvation, DNA damage, and oxidative stress).
Activated sirtuins subsequently stimulate specific transcriptional programs to make
mitochondrial oxidative metabolism more efficient in the fight against oxidative
stress or regulate proteins responsible for DNA repair after damage. As a result of
their multifunctional involvement in cellular metabolism, dysregulation and aberrant
expression of sirtuins have been observed in various cancers. Sirtuins play a dual role
*Corresponding author: in carcinogenesis, acting as either oncogenes or tumor suppressors and affecting the
Roman Beňačka
(roman.benacka@upjs.sk) proliferation, apoptosis, and survival of cancerous cells.
Citation: Szabóová D, Guľašová Z,
Hertelyová Z, Beňačka R. Keywords: Sirtuins; Oxidative stress; Cancer
Understanding the fundamental
mechanisms and conditions of the
tumor-suppressive and oncogenic
roles of sirtuins in cancer: A review.
Gene Protein Dis. 2024;3(4):4100. 1. Introduction
doi: 10.36922/gpd.4100
Received: July 1, 2024 Silent information regulators (SIRTs) or sirtuins are a family of proteins that have attracted
Accepted: September 5, 2024 significant interest in biology and medicine research due to their involvement in cellular
Published Online: October 10, 2024 metabolism, particularly in processes related to aging, stress resistance, starvation, and
1
Copyright: © 2024 Author(s). survival (Figure 1). Sirtuins are nicotinamide adenine dinucleotide (NAD)-dependent
This is an Open-Access article histone deacetylases, and different types of sirtuins possess mono–adenosine diphosphate
distributed under the terms of the
Creative Commons Attribution (ADP)-ribosyltransferase, deacylase, demyristoylase, demalonylase, desuccinylase, and
License, permitting distribution, depalmitoylase activities. The enzymatic activity of sirtuins is dependent on NAD,
and reproduction in any medium, and during the deacetylation reaction, histone lysines are deacetylated, and NAD is
provided the original work is
properly cited. consumed in a process called hydrolysis. Simultaneously, the acetyl group bound to lysine
is transferred from the target structure to the 2’-OH position of ADP-ribose, yielding
Publisher’s Note: AccScience
Publishing remains neutral with 2’-O-acetyl-ADP-ribose and nicotinamide (3-pyridinecarboxamide or niacinamide). 2
regard to jurisdictional claims in
published maps and institutional Changes in the acetylation status of lysine residues of histones represents a form of
affiliations. epigenetic regulation of gene expression that can cause activation or deactivation of

Volume 3 Issue 4 (2024) 1 doi: 10.36922/gpd.4100