Sirtuins: Molecular Traffic Lights in the Crossroad of Oxidative Stress, Chromatin Remodeling, and Transcription

Abstract

Transcription is regulated by acetylation/deacetylation reactions of histone and nonhistone proteins mediated by enzymes called KATs and HDACs, respectively. As a major mechanism of transcriptional regulation, protein acetylation is a key controller of physiological processes such as cell cycle, DNA damage response, metabolism, apoptosis, and autophagy. The deacetylase activity of class III histone deacetylases or sirtuins depends on the presence of NAD+ (nicotinamide adenine dinucleotide), and therefore, their function is closely linked to cellular energy consumption. This activity of sirtuins connects the modulation of chromatin dynamics and transcriptional regulation under oxidative stress to cellular lifespan, glucose homeostasis, inflammation, and multiple aging-related diseases including cancer. Here we provide an overview of the recent developments in relation to the diverse biological activities associated with sirtuin enzymes and stress responsive transcription factors, DNA damage, and oxidative stress and relate the involvement of sirtuins in the regulation of these processes to oncogenesis. Since the majority of the molecular mechanisms implicated in these pathways have been described for Sirt1, this sirtuin family member is more extensively presented in this paper.

The role of SIRT6 in tumors

“…2,3 The vast effort of European investigators in standardizing MRD assessment by polymerase chain reaction (PCR) and flow cytometry merits recognition and credit. 4,5 At present, we have several independent quantitative monitoring strategies, namely, PCR on DNA targets, reverse transcription (RT)-PCR on abnormal ribonucleic acid (RNA) transcribed from fusion genes or overexpression of normal messenger (m)RNA, and flow cytometry.…”

“…2 In mammalian cells, the Sirtuin family is composed of seven members that show different subcellular localization and functions (transcription, metabolism, fat mobilization, DNA repair, stress responses, apoptosis, tumorigenesis and aging), 3,4 and conserve the catalytic domain and the NAD + binding site. 5 In cancer and agingassociated pathways, SIRT6 is crucial since it prevents genomic instability, maintains telomere integrity, and regulates metabolic homeostasis and DNA repair.…”

Roles of Reactive Oxygen Species in Rheumatoid Arthritis Pathogenesis

“…NF-κB signaling is activated during aging [52] and is a potent inducer of the expression of several NADPH oxidase components including gp91phox and p22phox [53]. SIRT1 has also been suggested as a potent inhibitor of NF-κB signaling by suppressing oxidative stress and inflammatory responses [54]. In response to oxidative stress SIRT1 induced antioxidant expression via forkhead box O (FoxO) pathways.…”

Insulin resistance pathogenesis in metabolic obesity

“…АФК участвуют в важных биологических реакциях, однако их чрезмерная продукция и накопление могут привести к состоянию окислительного стресса [2,20,21]. Так, ИР сопровождается нарушением метаболизма АФК, что приводит к развитию оксидативного стресса [22].…”