SIRT4

Summary

Gene Symbol: SIRT4
Description: sirtuin 4
Alias: SIR2L4, NAD-dependent protein lipoamidase sirtuin-4, mitochondrial, NAD-dependent ADP-ribosyltransferase sirtuin-4, NAD-dependent protein deacetylase sirtuin-4, SIR2-like protein 4, regulatory protein SIR2 homolog 4, sir2-like 4, sirtuin type 4
Species: human
Products:     SIRT4

Top Publications

  1. Ahuja N, Schwer B, Carobbio S, Waltregny D, North B, Castronovo V, et al. Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase. J Biol Chem. 2007;282:33583-92 pubmed
    ..We report that human SIRT4 is localized to the mitochondria...
  2. Jeong S, Lee A, Lee J, Haigis M. SIRT4 protein suppresses tumor formation in genetic models of Myc-induced B cell lymphoma. J Biol Chem. 2014;289:4135-44 pubmed publisher
    ..Recently, the mitochondrial sirtuin SIRT4 has been reported to function as a tumor suppressor by regulating glutamine metabolism, suggesting that it might ..
  3. Csibi A, Fendt S, Li C, Poulogiannis G, Choo A, Chapski D, et al. The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4. Cell. 2013;153:840-54 pubmed publisher
    ..This regulation requires transcriptional repression of SIRT4, the mitochondrial-localized sirtuin that inhibits GDH...
  4. Laurent G, de Boer V, Finley L, Sweeney M, Lu H, Schug T, et al. SIRT4 represses peroxisome proliferator-activated receptor ? activity to suppress hepatic fat oxidation. Mol Cell Biol. 2013;33:4552-61 pubmed publisher
    ..We have uncovered a novel role for the mitochondrial sirtuin SIRT4 in the regulation of hepatic lipid metabolism during changes in nutrient availability...
  5. Michishita E, Park J, Burneskis J, Barrett J, Horikawa I. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell. 2005;16:4623-35 pubmed
    ..are associated with heterochromatic regions and nucleoli, respectively, where yeast Sir2 functions; 2) SIRT3, SIRT4, and SIRT5 are localized in mitochondria, an organelle that links aging and energy metabolism; 3) cellular p53 is ..
  6. Haigis M, Mostoslavsky R, Haigis K, Fahie K, Christodoulou D, Murphy A, et al. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell. 2006;126:941-54 pubmed
    ..Mammals have seven Sir2 homologs (SIRT1-7). We show that SIRT4 is a mitochondrial enzyme that uses NAD to ADP-ribosylate and downregulate glutamate dehydrogenase (GDH) activity...
  7. Chen Z, Lin J, Feng S, Chen X, Huang H, Wang C, et al. SIRT4 inhibits the proliferation, migration, and invasion abilities of thyroid cancer cells by inhibiting glutamine metabolism. Onco Targets Ther. 2019;12:2397-2408 pubmed publisher
    b>SIRT4, a protein localized in the mitochondria, is one of the least characteristic members of the sirtuin family...
  8. Wever C, Geoffrion D, Grande B, Yu S, Alcaide M, Lemaire M, et al. The genomic landscape of two Burkitt lymphoma cases and derived cell lines: comparison between primary and relapse samples. Leuk Lymphoma. 2018;59:2159-2174 pubmed publisher
    ..at relapse, affecting important pathways such as NFκB (IKBKB) and MEK/ERK (NRAS) signaling, glutamine metabolism (SIRT4), and RNA processing (ZFP36L2)...
  9. Hu Q, Qin Y, Ji S, Xu W, Liu W, Sun Q, et al. UHRF1 promotes aerobic glycolysis and proliferation via suppression of SIRT4 in pancreatic cancer. Cancer Lett. 2019;452:226-236 pubmed publisher
    ..correlation between UHRF1 and SIRT3-5 expression and found a significant negative correlation between UHRF1 and SIRT4. Further transcriptional and functional analysis demonstrates that SIRT4 is a downstream target of UHRF1 and ..

More Information

Publications102 found, 100 shown here

  1. Gui L, Wu H, Raza S, Schreurs N, Shah M. The effect of haplotypes in the promoter region of SIRT4 gene on the ultrasound traits in Qinchuan cattle. Trop Anim Health Prod. 2019;: pubmed publisher
    Sirtuin 4 (SIRT4) belongs to the mitochondrial sirtuin class of NAD+-dependent protein deacylases. This gene plays an important role in the regulation of lipid metabolism, cellular growth, and metabolism in mammals...
  2. Hada K, Hirota K, Inanobe A, Kako K, Miyata M, Araoi S, et al. Tricarboxylic acid cycle activity suppresses acetylation of mitochondrial proteins during early embryonic development in Caenorhabditis elegans. J Biol Chem. 2019;294:3091-3099 pubmed publisher
    ..Taken together, these results suggest the possibility that during early embryogenesis, acetyl-CoA consumption by the TCA cycle in C. elegans prevents protein hyperacetylation and thereby protects mitochondrial function. ..
  3. Lin S, Teng L, Lin Y, Miao L, Ge X, Hao J, et al. Molecular and functional characterization of sirt4 and sirt6 in Megalobrama amblycephala under high glucose metabolism. Comp Biochem Physiol B Biochem Mol Biol. 2019;231:87-97 pubmed publisher
    We analyzed the sequences of sirt4 and sirt6 and their changes in expression after oral glucose administration in blunt snout bream (Megalobrama amblycephala)...
  4. Hong J, Li S, Wang X, Mei C, Zan L. Study of expression analysis of SIRT4 and the coordinate regulation of bovine adipocyte differentiation by SIRT4 and its transcription factors. Biosci Rep. 2018;38: pubmed publisher
    ..b>SIRT4 is a mitochondrial sirtuin and has been shown to play a critical role in maintaining insulin secretion and glucose ..
  5. Wang Y, Du L, Liang X, Meng P, Bi L, Wang Y, et al. Sirtuin 4 Depletion Promotes Hepatocellular Carcinoma Tumorigenesis Through Regulating Adenosine-Monophosphate-Activated Protein Kinase Alpha/Mammalian Target of Rapamycin Axis in Mice. Hepatology. 2018;: pubmed publisher
    Sirtuin 4 (SIRT4) has been reported to play a vital role in the maintenance of glutamine catabolism and adenosine triphosphate (ATP) homeostasis, but its character in hepatocellular carcinomas (HCCs) remains obscure...
  6. Liu B, Che W, Xue J, Zheng C, Tang K, Zhang J, et al. SIRT4 prevents hypoxia-induced apoptosis in H9c2 cardiomyoblast cells. Cell Physiol Biochem. 2013;32:655-62 pubmed publisher
    ..Here, we report that the expression of SIRT4, a mitochondrial sirtuin, is markedly down-regulated in hypoxia-induced apoptosis of H9c2 cardiomyoblast cells...
  7. do Amaral M, Ueno M, Oliveira C, Borsonello N, Vanzela E, Ribeiro R, et al. Reduced expression of SIRT1 is associated with diminished glucose-induced insulin secretion in islets from calorie-restricted rats. J Nutr Biochem. 2011;22:554-9 pubmed publisher
    Alterations in food intake such as caloric restriction modulate the expression of SIRT1 and SIRT4 proteins that are involved in pancreatic β-cell function...
  8. Tao J, Zhang J, Ling Y, McCall C, Liu T. Mitochondrial Sirtuin 4 Resolves Immune Tolerance in Monocytes by Rebalancing Glycolysis and Glucose Oxidation Homeostasis. Front Immunol. 2018;9:419 pubmed publisher
    ..We report here that mitochondrial sirtuin 4 (SIRT4) physiologically breaks tolerance and resolves acute inflammation in human monocytes by coordinately reprogramming ..
  9. Li S, Zheng W. Mammalian Sirtuins SIRT4 and SIRT7. Prog Mol Biol Transl Sci. 2018;154:147-168 pubmed publisher
    ..e., SIRT1-7) thus far identified in mammals including humans, we know SIRT1/2/3/5/6 better than SIRT4/7 as for their enzymatic activities and the cellular roles of the reactions they catalyze...
  10. Laddha R, Mahajania M, Khadse A, Bajaj R, Jawade R, Choube S. Assessment of Sirtuin 3 and Sirtuin 4 Level in Patients with Diabetes Mellitus and Periodontitis: A Clinical Study. J Contemp Dent Pract. 2018;19:1199-1203 pubmed
    ..The SIRT 3 and SIRT 4 are useful indicators of glycemic level in patients with DM. The SIRT 3 and SIRT 4 in DM show variation in their level. Early assessment may be proved beneficial in patients who are not responding to other drugs. ..
  11. Deng R, Zhang P, Liu W, Zeng X, Ma X, Shi L, et al. HDAC is indispensable for IFN-γ-induced B7-H1 expression in gastric cancer. Clin Epigenetics. 2018;10:153 pubmed publisher
    ..that expression of B7-H1, HDAC1-3, 6-8, and 10 and SIRT1, 3, 5, and 6 was higher, and expression of HDAC5 and SIRT4 was lower in GC compared to that in normal gastric tissues; that HDAC3 and HDAC1 expression level significantly ..
  12. Xia X, Xiao C, Shan H. Facilitation of liver cancer SMCC7721 cell aging by sirtuin 4 via inhibiting JAK2/STAT3 signal pathway. Eur Rev Med Pharmacol Sci. 2017;21:1248-1253 pubmed
    ..Sirtuin 4 facilitates Adriamycin-induced aging of SMCC7721 liver cancer cells via inhibiting JAK2/STAT3 signal pathway, thus providing one novel anti-cancer strategy. ..
  13. Wang Y, Guo Y, Gao J, Yuan X. Tumor-suppressive function of SIRT4 in neuroblastoma through mitochondrial damage. Cancer Manag Res. 2018;10:5591-5603 pubmed publisher
    b>SIRT4 is a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent enzymes located in the mitochondria, and is involved in regulating energy metabolism, stress response, and cellular lifespan in mammalian cells...
  14. Gong J, Wang H, Lou W, Wang G, Tao H, Wen H, et al. Associations of sirtuins with clinicopathological parameters and prognosis in non-small cell lung cancer. Cancer Manag Res. 2018;10:3341-3356 pubmed publisher
    ..Our results suggested SIRT1, SIRT3, SIRT4, and SIRT7 were highly expressed in adeno-carcinoma (ADC) patients and female patients while SIRT5 were highly ..
  15. Huang P, Riordan S, Heruth D, Grigoryev D, Zhang L, Ye S. A critical role of nicotinamide phosphoribosyltransferase in human telomerase reverse transcriptase induction by resveratrol in aortic smooth muscle cells. Oncotarget. 2015;6:10812-24 pubmed
    ..Here, we report that resveratrol activates human nicotinamide phosphoribosyltransferase (NAMPT), SIRT4 and telomerase reverse transcriptase (hTERT) in human aortic smooth muscle cells...
  16. Tain Y, Leu S, Lee W, Wu K, Chan J. Maternal Melatonin Therapy Attenuated Maternal High-Fructose Combined with Post-Weaning High-Salt Diets-Induced Hypertension in Adult Male Rat Offspring. Molecules. 2018;23: pubmed publisher
    ..on HF/HS-induced hypertension related to regulating several nutrient-sensing signals, including Sirt1, Sirt4, Prkaa2, Prkab2, Pparg, and Ppargc1a...
  17. Pusalkar M, Suri D, Kelkar A, Bhattacharya A, Galande S, Vaidya V. Early stress evokes dysregulation of histone modifiers in the medial prefrontal cortex across the life span. Dev Psychobiol. 2016;58:198-210 pubmed publisher
    ..While specific histone modifiers (Kat2a, Smyd3, and Suv420h1) and the sirtuin, Sirt4 were downregulated across life within the mPFC of ES animals, namely at postnatal Day 21, 2 months, and 15 months ..
  18. Parihar P, Solanki I, Mansuri M, Parihar M. Mitochondrial sirtuins: emerging roles in metabolic regulations, energy homeostasis and diseases. Exp Gerontol. 2015;61:130-41 pubmed publisher
    ..Mitochondria inhabit three main types of sirtuins classified as Sirt3, Sirt4 and Sirt5...
  19. Elkhwanky M, Hakkola J. Extranuclear Sirtuins and Metabolic Stress. Antioxid Redox Signal. 2018;28:662-676 pubmed publisher
    Extranuclear sirtuins in cytosol (SIRT2) and mitochondria (SIRT3, SIRT4, and SIRT5) are key regulators of metabolic enzymes and the antioxidative defense mechanisms...
  20. Marchand A, Atassi F, Mougenot N, Clergue M, Codoni V, Berthuin J, et al. miR-322 regulates insulin signaling pathway and protects against metabolic syndrome-induced cardiac dysfunction in mice. Biochim Biophys Acta. 2016;1862:611-621 pubmed publisher
    ..Altogether, these results emphasize miR-322 as a new potential therapeutic target against cardiac consequences of metabolic syndrome, which represents an increasing burden in the western countries. ..
  21. Wang L, Li J, Guo L, Li P, Zhao Z, Zhou H, et al. Molecular link between glucose and glutamine consumption in cancer cells mediated by CtBP and SIRT4. Oncogenesis. 2018;7:26 pubmed publisher
    ..report indicated that CtBP increases GDH activity and promotes glutaminolysis through repressing the expression of SIRT4, a well-known mitochondrion-located factor that inhibits glutaminolysis pathway...
  22. Maeda S, Koya D, Araki S, Babazono T, Umezono T, Toyoda M, et al. Association between single nucleotide polymorphisms within genes encoding sirtuin families and diabetic nephropathy in Japanese subjects with type 2 diabetes. Clin Exp Nephrol. 2011;15:381-390 pubmed publisher
    ..We examined 52 SNPs within the SIRT genes (11 in SIRT1, 7 in SIRT2, 14 in SIRT3, 7 in SIRT4, 9 in SIRT5, and 4 in SIRT6) in 3 independent Japanese populations with type 2 diabetes (study 1: 747 cases (overt ..
  23. Shih J, Liu L, Mason A, Higashimori H, Donmez G. Loss of SIRT4 decreases GLT-1-dependent glutamate uptake and increases sensitivity to kainic acid. J Neurochem. 2014;131:573-81 pubmed publisher
    ..Loss of SIRT4 leads to a more severe reaction to kainic acid and decreased glutamate transporter expression and function in the ..
  24. Wong D, Soga T, Parhar I. Aging and chronic administration of serotonin-selective reuptake inhibitor citalopram upregulate Sirt4 gene expression in the preoptic area of male mice. Front Genet. 2015;6:281 pubmed publisher
    ..Age-related increases of sirt1, sirt4, sirt5, and sirt7 mRNA levels were observed in the POA of 52 weeks old mice...
  25. Klenke S, Renckhoff K, Engler A, Peters J, Frey U. Easy-to-use strategy for reference gene selection in quantitative real-time PCR experiments. Naunyn Schmiedebergs Arch Pharmacol. 2016;389:1353-1366 pubmed
    ..Target gene expression (Vegfa, Grk2, Sirt4, and Timp3) in H9c2 cells was analyzed following various interventions (hypoxia, hyperglycemia, and/or isoflurane ..
  26. Pusalkar M, Ghosh S, Jaggar M, Husain B, Galande S, Vaidya V. Acute and Chronic Electroconvulsive Seizures (ECS) Differentially Regulate the Expression of Epigenetic Machinery in the Adult Rat Hippocampus. Int J Neuropsychopharmacol. 2016;19: pubmed publisher
    ..and DNA modifiers, and methyl-CpG-binding proteins, with an overlapping pattern of gene regulation restricted to Sirt4, Mll3, Jmjd3, Gadd45b, Tet2, and Tet3...
  27. Oh H, Kwak J, Yang S, Gong M, Kim J, Rhee J, et al. Reciprocal regulation by hypoxia-inducible factor-2α and the NAMPT-NAD(+)-SIRT axis in articular chondrocytes is involved in osteoarthritis. Osteoarthritis Cartilage. 2015;23:2288-2296 pubmed publisher
    ..Among SIRT family members (SIRT1-7), SIRT2 and SIRT4 were positively associated with HIF-2α stability and transcriptional activity in chondrocytes...
  28. Zaganjor E, Vyas S, Haigis M. SIRT4 Is a Regulator of Insulin Secretion. Cell Chem Biol. 2017;24:656-658 pubmed publisher
    In a recent issue of Cell Metabolism, Anderson et al. (2017) report that SIRT4 regulates insulin sensitivity in the pancreas via activation of methylcrotonyl-CoA carboxylase 1 (MCCC1) by removal of dicarboxyacyl-lysine modifications...
  29. Wencel P, Lukiw W, Strosznajder J, Strosznajder R. Inhibition of Poly(ADP-ribose) Polymerase-1 Enhances Gene Expression of Selected Sirtuins and APP Cleaving Enzymes in Amyloid Beta Cytotoxicity. Mol Neurobiol. 2018;55:4612-4623 pubmed publisher
    ..Concomitantly, PJ-34 enhanced mRNA level of nuclear Sirt1, Sirt6, mitochondrial Sirt4, and Parp3 in PC12 cells subjected to AβOs toxicity...
  30. Drew J, Farquharson A, Horgan G, Williams L. Tissue-specific regulation of sirtuin and nicotinamide adenine dinucleotide biosynthetic pathways identified in C57Bl/6 mice in response to high-fat feeding. J Nutr Biochem. 2016;37:20-29 pubmed publisher
    ..Regulation of the SIRT/NAD system was associated with early (SIRT4, SIRT7, NAPRT1 and NMNAT2) and late phases (NMNAT3, NMRK2, ABCA1 and CD38) of glucose intolerance...
  31. Kamble P, Litvinov D, Aluganti Narasimhulu C, Jiang X, Parthasarathy S. Aspirin may influence cellular energy status. Eur J Pharmacol. 2015;749:12-9 pubmed publisher
    ..acid (SA) treatment resulted in generation of H2O2, which is known to be an inducer of mitochondrial gene Sirt4 and other downstream target genes of Sirt1...
  32. Simó Mirabet P, Bermejo Nogales A, Calduch Giner J, Pérez Sánchez J. Tissue-specific gene expression and fasting regulation of sirtuin family in gilthead sea bream (Sparus aurata). J Comp Physiol B. 2017;187:153-163 pubmed publisher
    ..Phylogenetic analysis showed three major clades corresponding to SIRT1-3, SIRT4-5, and SIRT6-7 that reflected the present hierarchy of vertebrates and the accepted classification of SIRTs...
  33. Roos C, Hagler M, Zhang B, Oehler E, Arghami A, Miller J. Transcriptional and phenotypic changes in aorta and aortic valve with aging and MnSOD deficiency in mice. Am J Physiol Heart Circ Physiol. 2013;305:H1428-39 pubmed publisher
    ..expression was relatively well-preserved in aorta from both genotypes, whereas expression of SIRT1, SIRT2, SIRT3, SIRT4, and SIRT6 were significantly reduced in the aortic valve...
  34. Ramatchandirin B, Sadasivam M, Kannan A, Prahalathan C. Sirtuin 4 Regulates Lipopolysaccharide Mediated Leydig Cell Dysfunction. J Cell Biochem. 2016;117:904-16 pubmed publisher
    ..The present study demonstrates that LPS causes mitochondrial dysfunction via suppression of sirtuin 4 (SIRT4); which in turn affects Leydig cell function by modulating steroidogenesis and apoptosis...
  35. Zeng G, Liu H, Wang H. Amelioration of myocardial ischemia-reperfusion injury by SIRT4 involves mitochondrial protection and reduced apoptosis. Biochem Biophys Res Commun. 2018;502:15-21 pubmed publisher
    Apoptosis and mitochondria dysfunction are key contributors to myocardial ischemia-reperfusion (MI-R) injury. SIRT4, a mitochondrial-localized sirtuin, controls cellular energy metabolism and stress response, and is abundantly present in ..
  36. Rouble A, Storey K. Characterization of the SIRT family of NAD+-dependent protein deacetylases in the context of a mammalian model of hibernation, the thirteen-lined ground squirrel. Cryobiology. 2015;71:334-43 pubmed publisher
    ..To assess this possibility, protein levels of the seven mammalian SIRTs (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6 and SIRT7), total SIRT activity, and the acetylation status of two downstream SIRT targets (SOD2K68 ..
  37. Temel M, Koç M, Ulutaş S, Göğebakan B. The expression levels of the sirtuins in patients with BCC. Tumour Biol. 2016;37:6429-35 pubmed publisher
    ..1, Sirt1.2, Sirt2, Sirt3, Sirt4, Sirt5, Sirt6, and Sirt7) were examined by real-time PCR. The results showed that expressions of SIRT1.1, SIRT1...
  38. Shi Q, Liu T, Zhang X, Geng J, He X, Nu M, et al. Decreased sirtuin 4 expression is associated with poor prognosis in patients with invasive breast cancer. Oncol Lett. 2016;12:2606-2612 pubmed
    ..Sirtuin 4 (SIRT4) is an important molecule that mediates the blockade of glutamine catabolism by inhibiting glutamate dehydrogenase...
  39. Wood J, Schwer B, Wickremesinghe P, Hartnett D, Burhenn L, Garcia M, et al. Sirt4 is a mitochondrial regulator of metabolism and lifespan in Drosophila melanogaster. Proc Natl Acad Sci U S A. 2018;115:1564-1569 pubmed publisher
    ..Here, we show the sole mitochondrial sirtuin in Drosophila melanogaster, Sirt4, regulates energy homeostasis and longevity...
  40. Carrico C, Meyer J, He W, Gibson B, Verdin E. The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications. Cell Metab. 2018;27:497-512 pubmed publisher
    ..Three protein deacylases, SIRT3, SIRT4, and SIRT5, reside in the mitochondria and remove these modifications from targeted proteins in an NAD+-..
  41. Chen L, Wang H, Gao F, Zhang J, Zhang Y, Ma R, et al. Functional genetic variants in the SIRT5 gene promoter in acute myocardial infarction. Gene. 2018;675:233-239 pubmed publisher
    ..Mitochondrial sirtuins, SIRT3, SIRT4 and SIRT5, function as critical regulators of mitochondrial metabolism, oxidative stress and cell survival...
  42. Sun H, Huang D, Liu G, Jian F, Zhu J, Zhang L. SIRT4 acts as a tumor suppressor in gastric cancer by inhibiting cell proliferation, migration, and invasion. Onco Targets Ther. 2018;11:3959-3968 pubmed publisher
    Previous study has proven that SIRT4 is downregulated in gastric cancer (GC), but the role of SIRT4 has not been clearly understood. The aim of our work was to explore in detail the function and mechanism of SIRT4 in GC...
  43. Guo L, Zhou S, Wei X, Liu Y, Chang X, Liu Y, et al. Acetylation of Mitochondrial Trifunctional Protein ?-Subunit Enhances Its Stability To Promote Fatty Acid Oxidation and Is Decreased in Nonalcoholic Fatty Liver Disease. Mol Cell Biol. 2016;36:2553-67 pubmed publisher
    ..Sirtuin 4 (SIRT4) has been identified as the deacetylase, deacetylating and destabilizing MTP?...
  44. Li Y, Zhou Y, Wang F, Chen X, Wang C, Wang J, et al. SIRT4 is the last puzzle of mitochondrial sirtuins. Bioorg Med Chem. 2018;26:3861-3865 pubmed publisher
    ..In mitochondrial sirtuins, SIRT4 was the last of less well-understood mitochondrial sirtuins especially for its robust enzymatic activity...
  45. Wu Y, Chen H, Lu J, Zhang M, Zhang R, Duan T, et al. Acetylation-dependent function of human single-stranded DNA binding protein 1. Nucleic Acids Res. 2015;43:7878-87 pubmed publisher
    ..Here, we determined that hSSB1 acetylation at K94 mediated by the acetyltransferase p300 and the deacetylases SIRT4 and HDAC10 impaired its ubiquitin-mediated degradation by proteasomes...
  46. Igci M, Kalender M, Borazan E, Bozgeyik I, Bayraktar R, Bozgeyik E, et al. High-throughput screening of Sirtuin family of genes in breast cancer. Gene. 2016;586:123-8 pubmed publisher
    ..Particularly, expressions of SIRT1 and SIRT4 were found to be significantly down-regulated in breast cancer tissues and SKBR3 breast cancer cells...
  47. Grande I, Amorim P, Freire A, Jallad R, Musolino N, Cescato V, et al. Differential gene expression of sirtuins between somatotropinomas and nonfunctioning pituitary adenomas. Pituitary. 2018;21:355-361 pubmed publisher
    ..4 and 40.5%, respectively, P < 0.01) as well as SIRT4 and SIRT7...
  48. Lin J, Kubota S, Mostoslavsky R, Apte R. Role of Sirtuins in Retinal Function Under Basal Conditions. Adv Exp Med Biol. 2018;1074:561-567 pubmed publisher
    ..Our results suggest that SIRT1, SIRT2, SIRT4, and SIRT6 are dispensable for retinal survival at baseline, as individual deletion of each of these sirtuins does ..
  49. Assadi Porter F, Reiland H, Sabatini M, Lorenzini L, Carnicelli V, Rogowski M, et al. Metabolic Reprogramming by 3-Iodothyronamine (T1AM): A New Perspective to Reverse Obesity through Co-Regulation of Sirtuin 4 and 6 Expression. Int J Mol Sci. 2018;19: pubmed publisher
    ..i>Sirt6 (a master gene regulator of glucose) and Gck (glucose kinase) and a decreased expression of Sirt4 (a negative regulator of fatty acids oxidation (FAO)), whereas in white adipose tissue only Sirt6 was ..
  50. Teng Y, Jing H, Aramsangtienchai P, He B, Khan S, Hu J, et al. Efficient demyristoylase activity of SIRT2 revealed by kinetic and structural studies. Sci Rep. 2015;5:8529 pubmed publisher
    ..Among the seven mammalian sirtuins, SIRT1-7, only SIRT1-3 possess efficient deacetylase activity in vitro, whereas SIRT4-7 possess very weak in vitro deacetylase activity...
  51. Tan Y, Xu Z, Tao J, Ni J, Zhao W, Lu J, et al. A SIRT4-like auto ADP-ribosyltransferase is essential for the environmental growth of Mycobacterium smegmatis. Acta Biochim Biophys Sin (Shanghai). 2016;48:145-52 pubmed publisher
    ..Here, a SIRT4 homologue MSMEG_4620 was identified and characterized in Mycobacterium smegmatis...
  52. Kida Y, Goligorsky M. Sirtuins, Cell Senescence, and Vascular Aging. Can J Cardiol. 2016;32:634-41 pubmed publisher
    ..SIRT1 and SIRT2 are localized in the nucleus and cytoplasm. SIRT3, SIRT4, and SIRT5 are mitochondrial, and SIRT6 and SIRT7 are nuclear...
  53. Lim R, Barker G, Menon R, Lappas M. A Novel Role for SIRT3 in Regulating Mediators Involved in the Terminal Pathways of Human Labor and Delivery. Biol Reprod. 2016;95:95 pubmed
    ..In this study, we determined the effect of term labor and pro-inflammatory cytokines on SIRT3, SIRT4, SIRT5, and SIRT7 expression in human myometrium...
  54. Xiao Y, Zhang X, Fan S, Cui G, Shen Z. MicroRNA-497 Inhibits Cardiac Hypertrophy by Targeting Sirt4. PLoS ONE. 2016;11:e0168078 pubmed publisher
    ..In addition, luciferase reporter assays demonstrated that Sirt4 was a direct target gene of miR-497...
  55. Celichowski P, Jopek K, Szyszka M, Tyczewska M, Malendowicz L, Rucinski M. Mitochondrial sirtuins in the rat adrenal gland: location within the glands of males and females, hormonal and developmental regulation of gene expressions. Folia Histochem Cytobiol. 2017;55:190-202 pubmed publisher
    ..These findings suggest that sirtuins expressed in mitochondria, Sirt3, Sirt4 and Sirt5, may be associated with adrenal steroidogenesis...
  56. Tain Y, Lee W, Wu K, Leu S, Chan J. Maternal High Fructose Intake Increases the Vulnerability to Post-Weaning High-Fat Diet-Induced Programmed Hypertension in Male Offspring. Nutrients. 2018;10: pubmed publisher
    ..Post-weaning high-fructose and high-fat diets similarly reduced Sirt4, Prkaa2, Prkag2, Ppara, Pparb, and Ppargc1a mRNA expression in offspring ..
  57. Kato Y, Kihara H, Fukui K, Kojima M. A ternary complex model of Sirtuin4-NAD+-Glutamate dehydrogenase. Comput Biol Chem. 2018;74:94-104 pubmed publisher
    Sirtuin4 (Sirt4) is one of the mammalian homologues of Silent information regulator 2 (Sir2), which promotes the longevity of yeast, C. elegans, fruit flies and mice...
  58. Frye R. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun. 2000;273:793-8 pubmed
    ..The seven human sirtuin genes include all four classes: SIRT1, SIRT2, and SIRT3 are class I, SIRT4 is class II, SIRT5 is class III, and SIRT6 and SIRT7 are class IV.
  59. Huang G, Cheng J, Yu F, Liu X, Yuan C, Liu C, et al. Clinical and therapeutic significance of sirtuin-4 expression in colorectal cancer. Oncol Rep. 2016;35:2801-10 pubmed publisher
    ..Recent studies indicate that SIRT4 acts as a tumor suppressor by regulating glutamine metabolism...
  60. Huynh F, Hu X, Lin Z, Johnson J, Hirschey M. Loss of sirtuin 4 leads to elevated glucose- and leucine-stimulated insulin levels and accelerated age-induced insulin resistance in multiple murine genetic backgrounds. J Inherit Metab Dis. 2018;41:59-72 pubmed publisher
    ..We recently showed that sirtuin 4 (SIRT4) removes glutaryl, 3-hydroxy-3-methylglutaryl, 3-methylglutaryl, and 3-methylglutaconyl modifications from lysine ..
  61. Inuzuka H, Gao D, Finley L, Yang W, Wan L, Fukushima H, et al. Acetylation-dependent regulation of Skp2 function. Cell. 2012;150:179-93 pubmed publisher
    ..Thus, our study identifies an acetylation-dependent regulatory mechanism governing Skp2 oncogenic function and provides insight into how cytoplasmic Skp2 controls cellular migration. ..
  62. Iwahara T, Bonasio R, Narendra V, Reinberg D. SIRT3 functions in the nucleus in the control of stress-related gene expression. Mol Cell Biol. 2012;32:5022-34 pubmed publisher
    ..Thus, SIRT3 exhibits a previously unappreciated role in the nucleus, modulating the expression of some stress-related and nuclear-encoded mitochondrial genes. ..
  63. Jeong S, Hwang S, Seong R. SIRT4 regulates cancer cell survival and growth after stress. Biochem Biophys Res Commun. 2016;470:251-256 pubmed publisher
    ..Although mitochondrial SIRT4 has been shown to be involved in cellular stress response and tumor suppression, its roles in survival and drug ..
  64. Yamamoto H, Schoonjans K, Auwerx J. Sirtuin functions in health and disease. Mol Endocrinol. 2007;21:1745-55 pubmed
    ..Here, we review some of the recent data related to the sirtuins and discuss their mode of action, their biological role in cellular and organismal models, and their possible association to age-related human diseases. ..
  65. Tang X, Chen X, Chen H, Liu D. Mitochondrial Sirtuins in cardiometabolic diseases. Clin Sci (Lond). 2017;131:2063-2078 pubmed publisher
    ..Three members of the Sirtuin family (SIRT3, SIRT4, and SIRT5) are located in the mitochondrion...
  66. Tarantino G, Finelli C, Scopacasa F, Pasanisi F, Contaldo F, Capone D, et al. Circulating levels of sirtuin 4, a potential marker of oxidative metabolism, related to coronary artery disease in obese patients suffering from NAFLD, with normal or slightly increased liver enzymes. Oxid Med Cell Longev. 2014;2014:920676 pubmed publisher
    The present study shows low circulating levels of SIRT4 in obese patients with nonalcoholic fatty liver disease mirroring its reduced mitochondrial expression in an attempt to increase the fat oxidative capacity and then the ..
  67. de Moura M, Uppala R, Zhang Y, Van Houten B, Goetzman E. Overexpression of mitochondrial sirtuins alters glycolysis and mitochondrial function in HEK293 cells. PLoS ONE. 2014;9:e106028 pubmed publisher
    SIRT3, SIRT4, and SIRT5 are mitochondrial deacylases that impact multiple facets of energy metabolism and mitochondrial function...
  68. Anderson K, Huynh F, Fisher Wellman K, Stuart J, Peterson B, Douros J, et al. SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion. Cell Metab. 2017;25:838-855.e15 pubmed publisher
    ..In contrast to the other mammalian sirtuins, the primary enzymatic activity of mitochondrial sirtuin 4 (SIRT4) and its overall role in metabolic control have remained enigmatic...
  69. Kumar S, Lombard D. For Certain, SIRT4 Activities!. Trends Biochem Sci. 2017;42:499-501 pubmed publisher
    Despite the fact that SIRT4 regulates important biological processes, its primary enzymatic activity has remained ambiguous. A recent study by Anderson, Huynh et al...
  70. Ho L, Titus A, Banerjee K, George S, Lin W, Deota S, et al. SIRT4 regulates ATP homeostasis and mediates a retrograde signaling via AMPK. Aging (Albany NY). 2013;5:835-49 pubmed
    ..Here, we report that the mitochondrial Sirtuin Sirt4 regulates mitochondrial ATP homeostasis...
  71. Mathias R, Greco T, Oberstein A, Budayeva H, Chakrabarti R, Rowland E, et al. Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity. Cell. 2014;159:1615-25 pubmed publisher
    ..Despite conserved deacetylase domains, mitochondrial SIRT4 and SIRT5 have little to no deacetylase activity, and a robust catalytic activity for SIRT4 has been elusive...
  72. Shen X, Li P, Xu Y, Chen X, Sun H, Zhao Y, et al. Association of sirtuins with clinicopathological parameters and overall survival in gastric cancer. Oncotarget. 2017;8:74359-74370 pubmed publisher
    ..The results suggested that SIRT4, SIRT6, and SIRT7 were associated with Lauren classification and SIRT3-5 were associated with pStage in gastric ..
  73. Irobi J, Van Impe K, Seeman P, Jordanova A, Dierick I, Verpoorten N, et al. Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy. Nat Genet. 2004;36:597-601 pubmed
    ..Expression of mutant HSPB8 in cultured cells promoted formation of intracellular aggregates. Our findings provide further evidence that mutations in heat-shock proteins have an important role in neurodegenerative disorders. ..
  74. Osborne B, Bentley N, Montgomery M, Turner N. The role of mitochondrial sirtuins in health and disease. Free Radic Biol Med. 2016;100:164-174 pubmed publisher
    ..SIRT3, SIRT4, and SIRT5 are found primarily located in the mitochondria, and are involved in many of the key processes of this ..
  75. Lang A, Anand R, Altinoluk Hambüchen S, Ezzahoini H, Stefanski A, Iram A, et al. SIRT4 interacts with OPA1 and regulates mitochondrial quality control and mitophagy. Aging (Albany NY). 2017;9:2163-2189 pubmed publisher
    The stress-responsive mitochondrial sirtuin SIRT4 controls cellular energy metabolism in a NAD+-dependent manner and is implicated in cellular senescence and aging...
  76. Pannek M, Simic Z, Fuszard M, Meleshin M, Rotili D, Mai A, et al. Crystal structures of the mitochondrial deacylase Sirtuin 4 reveal isoform-specific acyl recognition and regulation features. Nat Commun. 2017;8:1513 pubmed publisher
    ..b>Sirt4 locates to mitochondria and regulates fatty acid metabolism and apoptosis...
  77. Wu T, Liu Y, Fu Y, Liu X, Zhou X. Direct evidence of sirtuin downregulation in the liver of non-alcoholic fatty liver disease patients. Ann Clin Lab Sci. 2014;44:410-8 pubmed
    ..In contrast to the other SIRT genes, the expression of SIRT4 was upregulated...
  78. Huang G, Cui F, Yu F, Lu H, Zhang M, Tang H, et al. Sirtuin-4 (SIRT4) is downregulated and associated with some clinicopathological features in gastric adenocarcinoma. Biomed Pharmacother. 2015;72:135-9 pubmed publisher
    ..Recently, several studies have suggested that SIRT4 can regulate glutamine metabolism yet have tumor suppressor function too...
  79. Miyo M, Yamamoto H, Konno M, Colvin H, Nishida N, Koseki J, et al. Tumour-suppressive function of SIRT4 in human colorectal cancer. Br J Cancer. 2015;113:492-9 pubmed publisher
    b>SIRT4, which is localised in the mitochondria, is one of the least characterised members of the sirtuin family of nicotinamide adenine dinucleotide-dependent enzymes that play key roles in multiple cellular processes such as metabolism, ..
  80. Lang A, Grether Beck S, Singh M, Kuck F, Jakob S, Kefalas A, et al. MicroRNA-15b regulates mitochondrial ROS production and the senescence-associated secretory phenotype through sirtuin 4/SIRT4. Aging (Albany NY). 2016;8:484-505 pubmed
    ..Here, we link the mitochondrial sirtuin SIRT4 with cellular senescence, skin aging, and mitochondrial dysfunction...
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    ..In Caenorhabditis elegans, we found that knock-out of mitochondrial sirtuin sir-2.3, homologous to mammalian SIRT4, is protective in both chemical ischemia and hyperactive channel induced necrosis...
  82. Frye R. Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity. Biochem Biophys Res Commun. 1999;260:273-9 pubmed
    ..The SIRT1 sequence has the closest homology to the S. cerevisiae Sir2p. The SIRT4 and SIRT5 sirtuins more closely resemble prokaryotic sirtuin sequences...
  83. Song R, Xu W, Chen Y, Li Z, Zeng Y, Fu Y. The expression of Sirtuins 1 and 4 in peripheral blood leukocytes from patients with type 2 diabetes. Eur J Histochem. 2011;55:e10 pubmed publisher
    ..Immunocytochemical staining was used to detect SIRT1 and SIRT4 and reverse transcription polymerase chain reaction (RT-PCR) was used to detect SIRT1 or SIRT4 mRNA levels in PBLs...
  84. Savastano S, Di Somma C, Colao A, Barrea L, Orio F, Finelli C, et al. Preliminary data on the relationship between circulating levels of Sirtuin 4, anthropometric and metabolic parameters in obese subjects according to growth hormone/insulin-like growth factor-1 status. Growth Horm IGF Res. 2015;25:28-33 pubmed publisher
    The main components of GH/insulin-like growth factor (IGF)-1 axis and Sirtuin 4 (Sirt4), highly expressed in liver and skeletal muscle mitochondria, serve as active regulators of mitochondrial oxidative capacity with opposite functions...
  85. Bartosch C, Monteiro Reis S, Almeida Rios D, Vieira R, Castro A, Moutinho M, et al. Assessing sirtuin expression in endometrial carcinoma and non-neoplastic endometrium. Oncotarget. 2016;7:1144-54 pubmed publisher
    ..001) mRNA overexpression, whereas SIRT1 (p < 0.001), SIRT2 (p < 0.001), SIRT4 (p < 0.001) and SIRT5 (p < 0.001) were underexpressed...
  86. Mathias R, Greco T, Cristea I. Identification of Sirtuin4 (SIRT4) Protein Interactions: Uncovering Candidate Acyl-Modified Mitochondrial Substrates and Enzymatic Regulators. Methods Mol Biol. 2016;1436:213-39 pubmed publisher
    Recent studies have highlighted the three mitochondrial human sirtuins (SIRT3, SIRT4, and SIRT5) as critical regulators of a wide range of cellular metabolic pathways...
  87. Wang L, Zhou H, Wang Y, Cui G, Di L. CtBP maintains cancer cell growth and metabolic homeostasis via regulating SIRT4. Cell Death Dis. 2015;6:e1620 pubmed publisher
    ..CtBP) was found to have an essential role in promoting glutaminolysis by directly repressing the expression of SIRT4, a repressor of glutaminolysis by enzymatically modifying glutamate dehydrogenase in mitochondria, in cancer cells...
  88. Sandvoß M, Potthast A, von Versen Höynck F, Das A. HELLP Syndrome. Reprod Sci. 2017;24:568-574 pubmed publisher
    ..Protein levels of SIRT 4 were significantly higher in HUVECs from HELLP compared to control after 60 and 120 minutes of hypoxia. The NAD+ levels increased in a time-dependent manner. ..
  89. Fu L, Dong Q, He J, Wang X, Xing J, Wang E, et al. SIRT4 inhibits malignancy progression of NSCLCs, through mitochondrial dynamics mediated by the ERK-Drp1 pathway. Oncogene. 2017;36:2724-2736 pubmed publisher
    b>SIRT4 is well-known for its deacetylase activity in energy metabolism, but little is known about its roles in carcinogenesis...
  90. Chen X, Lai X, Wu C, Tian Q, Lei T, Pan J, et al. Decreased SIRT4 protein levels in endometrioid adenocarcinoma tissues are associated with advanced AJCC stage. Cancer Biomark. 2017;19:419-424 pubmed publisher
    ..Recently, several studies have suggested that SIRT4 not only regulates glutamine metabolism, but also serves as a tumor suppressor...
  91. Reiling E, van Vliet Ostaptchouk J, van t Riet E, van Haeften T, Arp P, Hansen T, et al. Genetic association analysis of 13 nuclear-encoded mitochondrial candidate genes with type II diabetes mellitus: the DAMAGE study. Eur J Hum Genet. 2009;17:1056-62 pubmed publisher
    ..After a meta-analysis, only one SNP in SIRT4 (rs2522138) remained significant (P=0.01)...
  92. Tao Y, Huang C, Huang Y, Hong L, Wang H, Zhou Z, et al. SIRT4 Suppresses Inflammatory Responses in Human Umbilical Vein Endothelial Cells. Cardiovasc Toxicol. 2015;15:217-23 pubmed publisher
    ..These include pro-inflammatory cytokines, cell adhesion molecules, and matrix degrading enzymes. SIRT4, a member of the sirtuin family, is a mitochondrial ADP-ribosyltransferase...