Multiple Roles of SIRT2 in Regulating Physiological and Pathological Signal Transduction

Abstract

Sirtuin 2 (SIRT2), as a member of the sirtuin family, has representative features of evolutionarily highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase activity. In addition, SIRT2, as the only sirtuin protein colocalized with tubulin in the cytoplasm, has its own functions and characteristics. In recent years, studies have increasingly shown that SIRT2 can participate in the regulation of gene expression and regulate signal transduction in the metabolic pathway mainly through its post-translational modification of target genes; thus, SIRT2 has become a key centre in the metabolic pathway and participates in the pathological process of metabolic disorder-related diseases. In this paper, it is discussed that SIRT2 can regulate all aspects of gene expression, including epigenetic modification, replication, transcription and translation, and post-translational modification, which enables SIRT2 to participate in energy metabolism in life activities, and it is clarified that SIRT2 is involved in metabolic process-specific signal transduction mechanisms. Therefore, SIRT2 can be involved in metabolic disorder-related inflammation and oxidative stress, thereby triggering the occurrence of metabolic disorder-related diseases, such as neurodegenerative diseases, tumours, diabetes, and cardiovascular diseases. Currently, although the role of SIRT2 in some diseases is still controversial, given the multiple roles of SIRT2 in regulating physiological and pathological signal transduction, SIRT2 has become a key target for disease treatment. It is believed that with increasing research, the clinical application of SIRT2 will be promoted.

Inflammatory Blood Signature Related to Common Psychological Comorbidity in Chronic Pain

“…AXIN1, for example, a regulator molecule of the Wnt signaling pathways [ 75 ], has been shown to correlate with disease severity in endometriosis [ 76 ]. SIRT2 has a wide range of regulatory functions ranging from neuronal to immunological and metabolic homeostasis [ 77 , 78 ]. Our study, together with other protein disease signature (PDS) studies, shows the importance of analyzing multiple inflammatory markers and comorbidities to explore a more complete picture of a disease.…”

The Pathogenesis of Diabetes

“…Jiang et al showed that SIRT2 decreased the acetylation of PEPCK1 and the association between PEPCK1 and UBR5, increased the stability of PEPCK1, and promoted gluconeogenesis [ 201 ]. It has also been shown that SIRT2 inhibition not only increased the stability of GKRP protein and promoted the degradation of ALDOA but also inhibited glucose-stimulated insulin secretion and reduced glycolytic flux by regulating the Akt/GSK3β/β-linked protein pathway in β-cells [ 202 ].…”

Exploring the Multi-Faceted Role of Sirtuins in Glioblastoma Pathogenesis and Targeting Options

“…Consequently, dysregulation of SIRT2 has been associated with a broad spectrum of diseases including metabolic and neurological disorders, cancer, and aging [ 51 , 52 ]. By forming a crosstalk between gene expression regulation and metabolic pathways, SIRT2 is involved in all aspects of cell metabolism, including lipogenesis, fatty acid oxidation, gluconeogenesis, and glycolysis [ 53 ]. SIRT2 promotes gluconeogenesis by deacetylating FOXO1 and Phosphoenolpyruvate Carboxykinase (PEPCK), enhances glycolysis by interacting with glycolytic enzymes (ALDOA, PGK1, ENO1, GAPDH, PFKP, PKM, LDH) [ 54 , 55 ], and regulates insulin secretion through the PI3K/AKT pathway [ 56 ].…”