Sirtuin 2 regulates cellular iron homeostasis via deacetylation of transcription factor NRF2

Journal of Clinical Investigation

Volumn 127, Issue 4, 2017, Pages 1505-1516

  Yang, Xiaoyan ^a   Park, Seong Hoon ^a,b   Chang, Hsiang Chun ^a   Shapiro, Jason S ^a   Vassilopoulos, Athanassios ^a   Sawicki, Konrad T ^a   Chen, Chunlei ^a   Shang, Meng ^a   Burridge, Paul W ^a   Epting, Conrad L ^a   Wilsbacher, Lisa D ^a   Jenkitkasemwong, Supak ^c   Knutson, Mitchell ^c   Gius, David ^a   Ardehali, Hossein ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

^b Korea Institute of Toxicology   (South Korea)

^c UNIVERSITY OF FLORIDA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FERROPORTIN 1; IRON; LYSINE; SIRTUIN 2; TRANSCRIPTION FACTOR NRF2; CATION TRANSPORT PROTEIN; METAL TRANSPORTING PROTEIN 1; NFE2L2 PROTEIN, HUMAN; SIRT2 PROTEIN, HUMAN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL LEVEL; CELL VIABILITY; CONTROLLED STUDY; DEACETYLATION; EMBRYO; GENE DELETION; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VITRO STUDY; IN VIVO STUDY; IRON DEFICIENCY; IRON METABOLISM; LIVER TISSUE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN STABILITY; ACETYLATION; ANIMAL; GENE EXPRESSION; GENETIC EPIGENESIS; HEK293 CELL LINE; HEP-G2 CELL LINE; HOMEOSTASIS; KNOCKOUT MOUSE; LIVER; METABOLISM; PHYSIOLOGY; PROTEIN PROCESSING; TRANSCRIPTION INITIATION;

ACETYLATION; ANIMALS; CATION TRANSPORT PROTEINS; EPIGENESIS, GENETIC; GENE EXPRESSION; HEK293 CELLS; HEP G2 CELLS; HOMEOSTASIS; HUMANS; IRON; LIVER; MICE, KNOCKOUT; NF-E2-RELATED FACTOR 2; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN STABILITY; SIRTUIN 2; TRANSCRIPTIONAL ACTIVATION;

EID: 85018689723     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI88574     Document Type: Article

References (40)

1. De Domenico I, McVey Ward D, Kaplan J. Regulation of iron acquisition and storage: consequences for iron-linked disorders. Nat Rev Mol Cell Biol. 2008;9(1):72-81.
2. Hentze MW, Muckenthaler MU, Galy B, Camaschella C. Two to tango: regulation of Mammalian iron metabolism. Cell. 2010;142(1):24-38.
3. Wang J, Pantopoulos K. Regulation of cellular iron metabolism. Biochem J. 2011;434(3):365-381.
4. Peyssonnaux C, et al. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J Clin Invest. 2007;117(7):1926-1932.
5. Bayeva M, et al. mTOR regulates cellular iron homeostasis through tristetraprolin. Cell Metab. 2012;16(5):645-657.
6. de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB. Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J. 2003;370(Pt 3):737-749.
7. Sauve AA, Wolberger C, Schramm VL, Boeke JD. The biochemistry of sirtuins. Annu Rev Biochem. 2006;75:435-465.
8. Du J, et al. Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science. 2011;334(6057):806-809.
9. Haigis MC, et al. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic ? cells. Cell. 2006;126(5):941-954.
10. Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell. 2005;16(10):4623-4635.
11. Pan PW, Feldman JL, Devries MK, Dong A, Edwards AM, Denu JM. Structure and biochemical functions of SIRT6. J Biol Chem. 2011;286(16):14575-14587.
12. Baur JA, Ungvari Z, Minor RK, Le Couteur DG, de Cabo R. Are sirtuins viable targets for improving healthspan and lifespan? Nat Rev Drug Discov. 2012;11(6):443-461.
13. Preyat N, Leo O. Sirtuin deacylases: a molecular link between metabolism and immunity. J Leukoc Biol. 2013;93(5):669-680.
14. Gomes P, Outeiro TF, Cavadas C. Emerging role of sirtuin 2 in the regulation of mammalian metabolism. Trends Pharmacol Sci. 2015;36(11):756-768.
15. Jiang W, et al. Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase. Mol Cell. 2011;43(1):33-44.
16. Wang F, Tong Q. SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma. Mol Biol Cell. 2009;20(3):801-808.
17. Rothgiesser KM, Erener S, Waibel S, Lüscher B, Hottiger MO. SIRT2 regulates NF-?B dependent gene expression through deacetylation of p65 Lys310. J Cell Sci. 2010;123(pt 24):4251-4258.
18. Serrano L, et al. The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation. Genes Dev. 2013;27(6):639-653.
19. Donmez G, Outeiro TF. SIRT1 and SIRT2: emerging targets in neurodegeneration. EMBO Mol Med. 2013;5(3):344-352.
20. Park SH, et al. SIRT2 is a tumor suppressor that connects aging, acetylome, cell cycle signaling, and carcinogenesis. Transl Cancer Res. 2012;1(1):15-21.
21. Zhang C. Essential functions of iron-requiring proteins in DNA replication, repair and cell cycle control. Protein Cell. 2014;5(10):750-760.
22. Wessling-Resnick M. Iron homeostasis and the inflammatory response. Annu Rev Nutr. 2010;30:105-122.
23. Fischer-Fodor E, Miklasova N, Berindan-Neagoe I, Saha B. Iron, inflammation and invasion of cancer cells. Clujul Med. 2015;88(3):272-277.
24. Ward RJ, Zucca FA, Duyn JH, Crichton RR, Zecca L. The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol. 2014;13(10):1045-1060.
25. Kim HS, et al. SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity. Cancer Cell. 2011;20(4):487-499.
26. Marro S, et al. Heme controls ferroportin1 (FPN1) transcription involving Bach1, Nrf2 and a MARE/ARE sequence motif at position-7007 of the FPN1 promoter. Haematologica. 2010;95(8):1261-1268.
27. Nairz M, et al. Nitric oxide-mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection. J Exp Med. 2013;210(5):855-873.
28. Hybertson BM, Gao B, Bose SK, McCord JM. Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. Mol Aspects Med. 2011;32(4-6):234-246.
29. Taguchi K, Motohashi H, Yamamoto M. Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution. Genes Cells. 2011;16(2):123-140.
30. Kawai Y, Garduño L, Theodore M, Yang J, Arinze IJ. Acetylation-deacetylation of the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) regulates its transcriptional activity and nucleocytoplasmic localization. J Biol Chem. 2011;286(9):7629-7640.
31. Jenkitkasemwong S, et al. SLC39A14 is required for the development of hepatocellular iron overload in murine models of hereditary hemochromatosis. Cell Metab. 2015;22(1):138-150.
32. Muhlenhoff U, et al. Cytosolic monothiol glutaredoxins function in intracellular iron sensing and trafficking via their bound iron-sulfur cluster (vol 12, pg 373, 2010). Cell Metab. 2014;20(4):696.
33. Jeong SM, Lee J, Finley LW, Schmidt PJ, Fleming MD, Haigis MC. SIRT3 regulates cellular iron metabolism and cancer growth by repressing iron regulatory protein 1. Oncogene. 2015;34(16):2115-2124.
34. Rao R, Georgieff MK. Iron in fetal and neonatal nutrition. Semin Fetal Neonatal Med. 2007;12(1):54-63.
35. Ma Q. Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol. 2013;53:401-426.
36. Ward JH, Jordan I, Kushner JP, Kaplan J. Heme regulation of HeLa cell transferrin receptor number. J Biol Chem. 1984;259(21):13235-13240.
37. Bories G, et al. Liver X receptor activation stimulates iron export in human alternative macrophages. Circ Res. 2013;113(11):1196-1205.
38. Brana C, Benham C, Sundstrom L. A method for characterising cell death in vitro by combining propidium iodide staining with immunohistochemistry. Brain Res Brain Res Protoc. 2002;10(2):109-114.
39. Vassilopoulos A, et al. SIRT3 deacetylates ATP synthase F1 complex proteins in response to nutrient-and exercise-induced stress. Antioxid Redox Signal. 2014;21(4):551-564.
40. Vichinsky E, et al. A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease. Br J Haematol. 2007;136(3):501-508.