Sirtuin-3 (SIRT3), a therapeutic target with oncogenic and tumor-suppressive function in cancer

Abstract

Sirtuin-3 (SIRT3), a major mitochondria NAD+-dependent deacetylase, may target mitochondrial proteins for lysine deacetylation and also regulate cellular functions. And, SIRT3 is an emerging instrumental regulator of the mitochondrial adaptive response to stress, such as metabolic reprogramming and antioxidant defense mechanisms. Accumulating evidence has recently demonstrated that SIRT3 may function as either oncogene or tumor suppressor on influencing cell death by targeting a series of key modulators and their relevant pathways in cancer. Thus, in this review, we present the structure, transcriptional regulation, and posttranslational modifications of SIRT3. Subsequently, we focus on highlighting the Janus role of SIRT3 with oncogenic or tumor-suppressive function in cancer, which may provide more new clues for exploring SIRT3 as a therapeutic target for drug discovery.

4-Hydroxynonenal Promotes Growth and Angiogenesis of Breast Cancer Cells through HIF-1α Stabilization

“…Sirtuin-3 (SIRT3), a major mitochondria NAD+-dependent deacetylase, was reported to destabilize HIF-1α (Chen et al, 2014). The activity of SIRT3 can be inhibited by 4-HNE (Fritz et al, 2011), we then investigated whether 4-HNE affects the levels of HIF-1α through SIRT3.…”

“…The stability of HIF-1α was regulated by its post-translational modifications such as hydroxylation, ubiquitination, acetylation, sumoylation and phosphorylation (Ke and Costa, 2006;Ulrich, 2007;van Hagen et al, 2010). Sirtuin-3 (SIRT3), a major mitochondria NAD+-dependent deacetylase, was reported to destabilize HIF-1α (Finley et al, 2011;Chen et al, 2014). Under the normoxic conditions, HIF-1α is degraded via the ubiquitin-proteasome pathway by binding of the von Hippel-Lindau tumor suppressor protein (pVHL) to the oxygen-dependent degradation domain (ODD) (Maxwell et al, 1999).…”

2-Methoxyestradiol Affects Mitochondrial Biogenesis Pathway and Succinate Dehydrogenase Complex Flavoprotein Subunit A in Osteosarcoma Cancer Cells

“…Figure 6 shows the 3D and 2D ligand receptor interactions demonstrated by molecular docking. Interestingly, the crucial interaction regions reported in the literature for known inhibitors (small molecules or peptides) were observed for 2-ME at both the canonical inhibitor and allosteric sites (42)(43)(44)(45)(46) Figure 6B-E.…”

Back on Track: New Perspectives on Cancer Cell Reprogramming

“…This metabolic switch is evidenced by a modulation in the expression of glycolysis enzymes, with a lowered expression of the glycolytic enzyme isoforms involved in the Warburg effect such as HK2, IDH2 and PKM2 [7] Concomitantly, we observe an increase in oxidative phosphorylation, as deduced by the decreased ATP content in differentiated cells compared to SH-SY5Y cells, following the in vitro inhibition of the mitochondrial electron transport chain. Restoration of mitochondrial activity is accompanied by a marked increase in Sirt3 activity [8].…”

“…This metabolic switch is evidenced by a modulation in the expression of glycolysis enzymes, with a lowered expression of the glycolytic enzyme isoforms involved in the Warburg effect such as HK2, IDH2 and PKM2 [7] Concomitantly, we observe an increase in oxidative phosphorylation, as deduced by the decreased ATP content in differentiated cells compared to SH-SY5Y cells, following the in vitro inhibition of the mitochondrial electron transport chain. Restoration of mitochondrial activity is accompanied by a marked increase in Sirt3 activity [8].This paper presents an alternative approach to cancer cell reprogramming towards a differentiated state, by skipping the iPSCs production passage usually found in the literature [9]. We supposed that cancer cells already showed sufficient stem-cell-like behavior to be ready for direct differentiation towards other germ layer lineages.…”