Mouse Sir2 Homolog SIRT6 Is a Nuclear ADP-ribosyltransferase
Open accessAbstract
Members of the Sir2 family of NAD-dependent protein deacetylases regulate diverse cellular processes including aging, gene silencing, and cellular differentiation. Here, we report that the distant mammalian Sir2 homolog SIRT6 is a broadly expressed, predominantly nuclear protein. Northern analysis of embryonic samples and multiple adult tissues revealed mouse SIRT6 (mSIRT6) mRNA peaks at day E11, persisting into adulthood in all eight tissues examined. At the protein level, mSIRT6 was readily detectable in the same eight tissue types, with the highest levels in muscle, brain, and heart. Subcellular localization studies using both C- and N-terminal green fluorescent protein fusion proteins showed mSIRT6-green fluorescent protein to be a predominantly nuclear protein. Indirect immunofluorescence using antibodies to two different mSIRT6 epitopes confirmed that endogenous mSIRT6 is also largely nuclear. Consistent with previous findings, we did not observe any NAD+-dependent protein deacetylase activity in preparations of mSIRT6. However, purified recombinant mSIRT6 did catalyze the robust transfer of radiolabel from [32P]NAD to mSIRT6. Two highly conserved residues within the catalytic core of the protein were required for this reaction. This reaction is most likely mono-ADP-ribosylation because only the modified form of the protein was recognized by an antibody specific to mono-ADP-ribose. Surprisingly, we observed that the catalytic mechanism of this reaction is intra-molecular, with individual molecules of mSIRT6 directing their own modification. These results provide the first characterization of a Sir2 protein from phylogenetic class IV.
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SIRT6 has multiple biochemical activities, including protein deacetylation and mono-ADP ribosylation.
“SIRT6 has multiple biochemical activities, including protein deacetylation22 and mono-ADP ribosylation19,29.”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [29]
SIRT4 and SIRT6 also function as ADP-ribosyltransferases.
“SIRT4 and SIRT6 also function as ADP-ribosyltransferases, indicating that sirtuins contribute to cell regulation also through mechanisms beyond modulation of protein acetylation, which require further investigation17,18.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [18]
Cites
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
Imai, S.-I., Armstrong, C. M., Kaeberlein, M., & Guarente, L. (2000) · Nature · doi:10.1038/35001622 · Cited by 3,510 · see citing works
Self-citationStress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., Tran, H., Ross, S. E., Mostoslavsky, R., Cohen, H. Y., et al. (2004) · Science · doi:10.1126/science.1094637 · Cited by 3,239 · see citing works
Kaeberlein, M., McVey, M., & Guarente, L. (1999) · Genes & Development · doi:10.1101/gad.13.19.2570 · Cited by 2,253 · see citing works
Self-citationSirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ
Picard, F., Kurtev, M. V., Chung, N., Topark‐Ngarm, A., Senawong, T., de Oliveira, R. M., Leid, M. E., McBurney, M. W., & Guarente, L. (2004) · Nature · doi:10.1038/nature02583 · Cited by 1,943 · see citing works
Self-citationIncreased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
Tissenbaum, H. A., & Guarente, L. (2001) · Nature · doi:10.1038/35065638 · Cited by 1,918 · see citing works
Self-citationSirtuin activators mimic caloric restriction and delay ageing in metazoans
Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M., & Sinclair, D. (2004) · Nature · doi:10.1038/nature02789 · Cited by 1,868 · see citing works
Lin, S.-J., Defossez, P.-A., & Guarente, L. (2000) · Science · doi:10.1126/science.289.5487.2126 · Cited by 1,775 · see citing works
Self-citationThe Human Sir2 Ortholog, SIRT2, Is an NAD+-Dependent Tubulin Deacetylase
North, B. J., Marshall, B. L., Borra, M. T., Denu, J. M., & Verdin, E. M. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00038-8 · Cited by 1,542 · see citing works
The Sir2 Family of Protein Deacetylases
Blander, G., & Guarente, L. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073651 · Cited by 1,496 · see citing works
Self-citationPhylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins
Frye, R. A. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3000 · Cited by 1,409 · see citing works
Sir2 mediates longevity in the fly through a pathway related to calorie restriction
Rogina, B., & Helfand, S. L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404184101 · Cited by 1,361 · see citing works
Mammalian SIRT1 Represses Forkhead Transcription Factors
Motta, M. C., Divecha, N., Lemieux, M. E., Kamel, C., Chen, D., Gu, W. J., Bultsma, Y., McBurney, M. W., & Guarente, L. (2004) · Cell · doi:10.1016/s0092-8674(04)00126-6 · Cited by 1,351 · see citing works
Self-citationFrye, R. A. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0897 · Cited by 809 · see citing works
Calorie restriction extends yeast life span by lowering the level of NADH
Lin, S.-J., Ford, E., Haigis, M., Liszt, G., & Guarente, L. (2004) · Genes & Development · doi:10.1101/gad.1164804 · Cited by 632 · see citing works
Self-citationSirtuins: Sir2-related NAD-dependent protein deacetylases.
North, B. J., & Verdin, E. M. (2004) · Genome biology · doi:10.1186/gb-2004-5-5-224 · Cited by 568 · see citing works
Tanner, K. G., Landry, J. W., Sternglanz, R., & Denu, J. M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.250422697 · Cited by 557 · see citing works
Genetics and the Specificity of the Aging Process
Hekimi, S., & Guarente, L. (2003) · Science · doi:10.1126/science.1082358 · Cited by 434 · see citing works
Self-citationAn Enzymatic Activity in the Yeast Sir2 Protein that Is Essential for Gene Silencing
Tanny, J. C., Dowd, G. J., Huang, J., Hilz, H., & Moazed, D. (1999) · Cell · doi:10.1016/s0092-8674(00)81671-2 · Cited by 391 · see citing works
Structure of the histone deacetylase SIRT2.
Finnin, M. S., Donigian, J. R., & Pavletich, N. P. (2001) · Nature Structural Biology · doi:10.1038/89668 · Cited by 376 · see citing works
Functional aspects of protein mono‐ADP‐ribosylation
Corda, D., & Girolamo, M. D. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg209 · Cited by 294 · see citing works
Nitric oxide stimulates auto-ADP-ribosylation of glyceraldehyde-3-phosphate dehydrogenase.
Zhang, J., & Snyder, S. H. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.20.9382 · Cited by 283 · see citing works
The molecular biology of the SIR proteins
Gasser, S. M., & Cockell, M. M. (2001) · Gene · doi:10.1016/s0378-1119(01)00741-7 · Cited by 263 · see citing works
Tanny, J. C., & Moazed, D. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.2.415 · Cited by 242 · see citing works
Bitterman, K. J., Medvedik, O., & Sinclair, D. A. (2003) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.67.3.376-399.2003 · Cited by 236 · see citing works
Sauve, A. A., & Schramm, V. L. (2004) · Current Medicinal Chemistry · doi:10.2174/0929867043455675 · Cited by 74 · see citing works
Auto-ADP-ribosylation of Pseudomonas aeruginosa ExoS
Riese, M. J., Goehring, U.-M., Ehrmantraut, M. E., Moss, J., Barbieri, J. T., Aktories, K., & Schmidt, G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109039200 · Cited by 64 · see citing works
Meyer, T. F., & Hilz, H. (1986) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1986.tb09471.x · Cited by 56 · see citing works
Armstrong, C. M., Kaeberlein, M. R., Imai, S., & Guarente, L. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.01-10-0482 · Cited by 55 · see citing works
Self-citationKain, S. R., Mai, K., & Sinai, P. (1994) · PubMed · Cited by 52 · see citing works
Weng, B., Thompson, W. C., Kim, H., Levine, R. L., & Moss, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.45.31797 · Cited by 36 · see citing works
糸賀基, Tsuchiya, M., Ishino, H., & Shimoyama, M. (1997) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a021692 · Cited by 11 · see citing works
Flagged first, then by citations
Cited by
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Reactive oxygen species, cellular redox systems, and apoptosis
Circu, M. L., & Aw, T. Y. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.12.022 · Cited by 3,340 · see citing works
Mammalian Sirtuins: Biological Insights and Disease Relevance
Haigis, M. C., & Sinclair, D. A. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092250 · Cited by 2,085 · see citing works
Sirtuins as regulators of metabolism and healthspan
Houtkooper, R. H., Pirinen, E., & Auwerx, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3293 · Cited by 2,008 · see citing works
Sirtuins in mammals: insights into their biological function
Michán, S., & Sinclair, D. A. (2007) · Biochemical Journal · doi:10.1042/bj20070140 · Cited by 1,719 · see citing works
Cantó, C., Menzies, K. J., & Auwerx, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.023 · Cited by 1,648 · see citing works
Genomic Instability and Aging-like Phenotype in the Absence of Mammalian SIRT6
Mostoslavsky, R., Chua, K. F., Lombard, D. B., Pang, W. W., Fischer, M. R., Gellon, L., Liu, P., Mostoslavsky, G., Franco, S., Murphy, M. M., et al. (2006) · Cell · doi:10.1016/j.cell.2005.11.044 · Cited by 1,637 · see citing works
Self-citationNAD+ metabolism and its roles in cellular processes during ageing
Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00313-x · Cited by 1,617 · see citing works
Sirt5 Is a NAD-Dependent Protein Lysine Demalonylase and Desuccinylase
Du, J., Zhou, Y., Su, X., Yu, J. J., Khan, S., Jiang, H., Kim, J., Woo, J., Kim, J. H., Choi, B. H., et al. (2011) · Science · doi:10.1126/science.1207861 · Cited by 1,429 · see citing works
Michishita, E., Park, J. Y., Burneskis, J. M., Barrett, J. C., & Horikawa, I. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-01-0033 · Cited by 1,364 · see citing works
Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction
Haigis, M. C., & Guarente, L. P. (2006) · Genes & Development · doi:10.1101/gad.1467506 · Cited by 1,295 · see citing works
Self-citationHaigis, M. C., Mostoslavsky, R., Haigis, K. M., Fahie, K., Christodoulou, D. C., Murphy, A. J., Valenzuela, D. M., Yancopoulos, G. D., Karow, M., Blander, G., et al. (2006) · Cell · doi:10.1016/j.cell.2006.06.057 · Cited by 1,162 · see citing works
Self-citationTargeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials
Cheng, Y., He, C., Wang, M., Ma, X., Mo, F., Yang, S., Han, J., & Wei, X. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0095-0 · Cited by 1,097 · see citing works
NAD+ metabolism in health and disease
Belenky, P. A., Bogan, K. L., & Brenner, C. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.11.006 · Cited by 983 · see citing works
The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways
Houtkooper, R. H., Cantó, C., Wanders, R. J., & Auwerx, J. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0026 · Cited by 899 · see citing works
Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence
Rajman, L., Chwalek, K., & Sinclair, D. A. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.011 · Cited by 865 · see citing works
SIRT6 Promotes DNA Repair Under Stress by Activating PARP1
Mao, Z., Hine, C., Tian, X., Van Meter, M., Au, M., Vaidya, A., Seluanov, A., & Gorbunova, V. (2011) · Science · doi:10.1126/science.1202723 · Cited by 867 · see citing works
Toward a unified nomenclature for mammalian ADP-ribosyltransferases
Hottiger, M. O., Hassa, P. O., Lüscher, B., Schuler, H., & Koch‐Nolte, F. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.12.003 · Cited by 814 · see citing works
Sauve, A. A., Wolberger, C., Schramm, V. L., & Boeke, J. D. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133500 · Cited by 763 · see citing works
Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going?
Hassa, P. O., Haenni, S. S., Elser, M., & Hottiger, M. O. (2006) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00040-05 · Cited by 682 · see citing works
Sirtuins in aging and age-related disease
Longo, V. D., & Kennedy, B. K. (2006) · Cell · doi:10.1016/j.cell.2006.07.002 · Cited by 628 · see citing works
Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription
Ford, E., Voit, R., Liszt, G., Magin, C., Grummt, I., & Guarente, L. (2006) · Genes & Development · doi:10.1101/gad.1399706 · Cited by 629 · see citing works
Self-citationSirtuins: critical regulators at the crossroads between cancer and aging
Saunders, L. R., & Verdin, E. M. (2007) · Oncogene · doi:10.1038/sj.onc.1210616 · Cited by 569 · see citing works
(2010) · doi:10.1016/j.cmet.2010.06.009 · Cited by 512 · see citing works
SIRT1 in Neurodevelopment and Brain Senescence
Herskovits, A. Z., & Guarente, L. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.028 · Cited by 493 · see citing works
Self-citationSIRT2 Regulates Adipocyte Differentiation through FoxO1 Acetylation/Deacetylation
Jing, E., Gesta, S., & Kahn, C. R. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.07.003 · Cited by 490 · see citing works
Van Meter, M., Kashyap, M., Rezazadeh, S., Geneva, A. J., Morello, T. D., Seluanov, A., & Gorbunova, V. (2014) · Nature Communications · doi:10.1038/ncomms6011 · Cited by 455 · see citing works
“SIRT6 has multiple biochemical activities, including protein deacetylation 22 and mono-ADP ribosylation 19,29 .”
Targeting Sirtuin 1 to Improve Metabolism: All You Need Is NAD+?
Cantó, C., & Auwerx, J. (2012) · Pharmacological Reviews · doi:10.1124/pr.110.003905 · Cited by 433 · see citing works
SIRT Inhibitors Induce Cell Death and p53 Acetylation through Targeting Both SIRT1 and SIRT2
Peck, B., Chen, C.-Y., Ho, K.-K., Fruscia, P. D., Myatt, S., Coombes, R., Fuchter, M., Hsiao, C.-D., & Lam, E. (2010) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0971 · Cited by 427 · see citing works
Sirtuins — novel therapeutic targets to treat age-associated diseases
Lavu, S., Boss, O., Elliott, P. J., & Lambert, P. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2665 · Cited by 425 · see citing works
Regulation of Insulin Secretion by SIRT4, a Mitochondrial ADP-ribosyltransferase
Ahuja, N., Schwer, B., Carobbio, S., Waltregny, D., North, B. J., Castronovo, V., Maechler, P., & Verdin, E. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m705488200 · Cited by 422 · see citing works
Sirtuins: The ‘ <i>magnificent seven</i> ’, function, metabolism and longevity
Dali‐Youcef, N., Lagouge, M., Froelich, S., Koehl, C., Schoonjans, K., & Auwerx, J. (2007) · Annals of Medicine · doi:10.1080/07853890701408194 · Cited by 402 · see citing works
SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling
Toiber, D., Erdel, F., Bouazoune, K., Silberman, D. M., Zhong, L., Mulligan, P., Sebastian, C., Cosentino, C., Martinez-Pastor, B., Giacosa, S., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.06.018 · Cited by 381 · see citing works
Li, L., Shi, L., Yang, S., Yan, R., Zhang, D., Yang, J., He, L., Li, W., Yi, X., Sun, L., et al. (2016) · Nature Communications · doi:10.1038/ncomms12235 · Cited by 392 · see citing works
Chemical mechanisms of histone lysine and arginine modifications
Smith, B. C., & Denu, J. M. (2009) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2008.06.005 · Cited by 390 · see citing works
Are sirtuins viable targets for improving healthspan and lifespan?
Baur, J. A., Ungvari, Z. I., Minor, R. K., Couteur, D. G. L., & de Cabo, R. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3738 · Cited by 389 · see citing works
SIRT6 is responsible for more efficient DNA double-strand break repair in long-lived species
Tian, X., Firsanov, D., Zhang, Z., Cheng, Y., Luo, L., Tombline, G., Tan, R., Simon, M., Henderson, S., Steffan, J., et al. (2019) · Cell · doi:10.1016/j.cell.2019.03.043 · Cited by 353 · see citing works
Seven sirtuins for seven deadly diseases ofaging
Morris, B. J. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.10.525 · Cited by 380 · see citing works
Lysine Acetylation Goes Global: From Epigenetics to Metabolism and Therapeutics
Ali, I., Conrad, R. J., Verdin, E. M., & Ott, M. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00181 · Cited by 366 · see citing works
Regulation of intermediary metabolism by protein acetylation
Guan, K., & Xiong, Y. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.09.003 · Cited by 353 · see citing works
Interphase Nucleo-Cytoplasmic Shuttling and Localization of SIRT2 during Mitosis
North, B. J., & Verdin, E. M. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000784 · Cited by 326 · see citing works
The Sir2 family of protein deacetylases
Denu, J. M. (2005) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2005.08.010 · Cited by 325 · see citing works
Structure and Biochemical Functions of SIRT6
Pan, P. W., Feldman, J. L., Devries, M., Dong, A., Edwards, A. M., & Denu, J. M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.218990 · Cited by 311 · see citing works
SIRT6 protects against pathological damage caused by diet‐induced obesity
Kanfi, Y., Peshti, V., Gil, R., Naiman, S., Nahum, L., Levin, E., Kronfeld‐Schor, N., & Cohen, H. Y. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2009.00544.x · Cited by 311 · see citing works
Van Gool, F., Gallí, M., Gueydan, C., Kruys, V., Prevot, P.-P., Bedalov, A., Mostoslavsky, R., Alt, F. W., De Smedt, T., & Leo, O. (2009) · Nature Medicine · doi:10.1038/nm.1906 · Cited by 285 · see citing works
Nakagawa, T., & Guarente, L. (2011) · Journal of Cell Science · doi:10.1242/jcs.081067 · Cited by 289 · see citing works
Self-citationEnergy metabolism in adult neural stem cell fate
Rafalski, V. A., & Brunet, A. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.10.007 · Cited by 280 · see citing works
Sirtuins in Epigenetic Regulation
Jing, H., & Lin, H. (2015) · Chemical Reviews · doi:10.1021/cr500457h · Cited by 271 · see citing works
SIRT1 Regulates the Function of the Nijmegen Breakage Syndrome Protein
Yuan, Z., Zhang, X. M., Sengupta, N., Lane, W. S., & Seto, E. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.05.029 · Cited by 271 · see citing works
Hodawadekar, S. C., & Marmorstein, R. (2007) · Oncogene · doi:10.1038/sj.onc.1210619 · Cited by 271 · see citing works
The Sirtuin family: therapeutic targets to treat diseases of aging
Milne, J. C., & Denu, J. M. (2008) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2008.01.019 · Cited by 271 · see citing works
Functions of the sirtuin deacylase SIRT5 in normal physiology and pathobiology
Kumar, S., & Lombard, D. B. (2018) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2018.1458071 · Cited by 264 · see citing works
SIRT6: Novel Mechanisms and Links to Aging and Disease
Tasselli, L., Zheng, W., & Chua, K. F. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2016.10.002 · Cited by 267 · see citing works
Structural Basis of Inhibition of the Human NAD+-Dependent Deacetylase SIRT5 by Suramin
Schuetz, A., Min, J., Antoshenko, T., Wang, C.-L., Allali‐Hassani, A., Dong, A., Loppnau, P., Vedadi, M., Bochkarev, A. V., Sternglanz, R., et al. (2007) · Structure · doi:10.1016/j.str.2007.02.002 · Cited by 264 · see citing works
Regulation of Akt Signaling by Sirtuins
Pillai, V. B., Sundaresan, N. R., & Gupta, M. P. (2014) · Circulation Research · doi:10.1161/circresaha.113.300536 · Cited by 260 · see citing works
Emerging Role of Sirtuin 2 in the Regulation of Mammalian Metabolism
Gomes, P., Outeiro, T. F., & Cavadas, C. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.08.001 · Cited by 253 · see citing works
The sirtuin SIRT6 deacetylates H3 K56Ac in vivo to promote genomic stability
Yang, B., Zwaans, B. M. M., Eckersdorff, M., & Lombard, D. B. (2009) · Cell Cycle · doi:10.4161/cc.8.16.9329 · Cited by 254 · see citing works
Sirtinol promotes PEPCK1 degradation and inhibits gluconeogenesis by inhibiting deacetylase SIRT2
Zhang, M., Pan, Y., Dorfman, R. G., Yin, Y., Zhou, Q., Huang, S. H., Liu, J., & Zhao, S. (2017) · Scientific Reports · doi:10.1038/s41598-017-00035-9 · Cited by 253 · see citing works
The Substrate Specificity of Sirtuins
Bheda, P., Jing, H., Wolberger, C., & Lin, H. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014537 · Cited by 247 · see citing works
Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes
Cantó, C., Sauve, A. A., & Bai, P. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2013.01.004 · Cited by 246 · see citing works
Mitochondrial sirtuins, metabolism, and aging
Ji, Z., Liu, G., & Qu, J. T. (2021) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2021.11.005 · Cited by 246 · see citing works
Dual control of mitochondrial biogenesis by sirtuin 1 and sirtuin 3
Brenmoehl, J., & Hoeflich, A. (2013) · Mitochondrion · doi:10.1016/j.mito.2013.04.002 · Cited by 240 · see citing works
Sorting out functions of sirtuins in cancer
Roth, M., & Chen, W. (2013) · Oncogene · doi:10.1038/onc.2013.120 · Cited by 239 · see citing works
Sirtuin regulation in aging and injury
Poulose, N., & Raju, R. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.08.017 · Cited by 236 · see citing works
Protein Lysine Acylation and Cysteine Succination by Intermediates of Energy Metabolism
Lin, H., Su, X., & He, B. (2012) · ACS Chemical Biology · doi:10.1021/cb3001793 · Cited by 236 · see citing works
SIRT6, a Mammalian Deacylase with Multitasking Abilities
Chang, A. R., Ferrer, C. M., & Mostoslavsky, R. (2019) · Physiological Reviews · doi:10.1152/physrev.00030.2018 · Cited by 236 · see citing works
Huang, J.-Y., Hirschey, M. D., Shimazu, T., Ho, L., & Verdin, E. (2010) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2009.12.021 · Cited by 231 · see citing works
Kwon, H.-S., & Ott, M. (2008) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2008.08.001 · Cited by 227 · see citing works
Chen, S., Seiler, J., Santiago-Reichelt, M., Felbel, K., Grummt, I., & Voit, R. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.10.010 · Cited by 224 · see citing works
Sirtuin deacetylases in neurodegenerative diseases of aging
Herskovits, A. Z., & Guarente, L. (2013) · Cell Research · doi:10.1038/cr.2013.70 · Cited by 222 · see citing works
Self-citationProtective effects and mechanisms of sirtuins in the nervous system
Zhang, F., Wang, S., Gan, L., Vosler, P. S., Gao, Y., Zigmond, M. J., & Chen, J. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.09.001 · Cited by 211 · see citing works
Sirtuin/Sir2 Phylogeny, Evolutionary Considerations and Structural Conservation
Greiss, S., & Gartner, A. (2009) · Molecules and Cells · doi:10.1007/s10059-009-0169-x · Cited by 207 · see citing works
Crystal Structures of Human SIRT3 Displaying Substrate-induced Conformational Changes
Jin, L., Wei, W., Jiang, Y., Peng, H., Cai, J., Mao, C., Dai, H., Choy, W., Bemis, J. E., Jirousek, M. R., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.014928 · Cited by 208 · see citing works
The Role of Sirtuins in Cellular Homeostasis
Kupis, W., Pałyga, J., Tomal, E., & Niewiadomska, E. (2016) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-016-0492-6 · Cited by 200 · see citing works
The Role of Sirtuins in the Control of Metabolic Homeostasis
Yu, J., & Auwerx, J. H. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04952.x · Cited by 196 · see citing works
Mammalian Sirtuins and Energy Metabolism
Li, X., & Kazgan, N. (2011) · International Journal of Biological Sciences · doi:10.7150/ijbs.7.575 · Cited by 192 · see citing works
The human sirtuin family: Evolutionary divergences and functions
Vassilopoulos, A., Fritz, K. S., Petersen, D. R., & Gius, D. R. (2011) · Human Genomics · doi:10.1186/1479-7364-5-5-485 · Cited by 191 · see citing works
Sirtuins at the crossroads of stemness, aging, and cancer
O'Callaghan, C., & Vassilopoulos, A. (2017) · Aging Cell · doi:10.1111/acel.12685 · Cited by 187 · see citing works
Regulation of SIRT6 protein levels by nutrient availability
Kanfi, Y., Shalman, R., Peshti, V., Pilosof, S. N., Gozlan, Y. M., Pearson, K. J., Lerrer, B., Moazed, D., Marine, J., de Cabo, R., et al. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.01.019 · Cited by 187 · see citing works
Structural and Functional Analysis of Human SIRT1
Davenport, A. M., Huber, F. M., & Hoelz, A. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.10.009 · Cited by 181 · see citing works
Neural sirtuin 6 (Sirt6) ablation attenuates somatic growth and causes obesity
Schwer, B., Schumacher, B., Lombard, D. B., Xiao, C., Kurtev, M. V., Gao, J., Schneider, J. I., Chai, H., Bronson, R. T., Tsai, L., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016306107 · Cited by 176 · see citing works
Self-citationNAD+ biosynthesis, aging, and disease
Johnson, S., & Imai, S. (2018) · F1000Research · doi:10.12688/f1000research.12120.1 · Cited by 178 · see citing works
New PARP targets for cancer therapy
Vyas, S., & Chang, P. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3748 · Cited by 178 · see citing works
Pfister, J. A., Ma, C., Morrison, B. E., & D’Mello, S. R. (2008) · PLoS ONE · doi:10.1371/journal.pone.0004090 · Cited by 176 · see citing works
Hepatic SREBP-2 and cholesterol biosynthesis are regulated by FoxO3 and Sirt6
Tao, R., Xiong, X., DePinho, R. A., Deng, C., & Dong, X. C. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m039339 · Cited by 179 · see citing works
Emerging roles of SIRT6 in human diseases and its modulators
Liu, G., Chen, H., Liu, H., Zhang, W., & Zhou, J. (2020) · Medicinal Research Reviews · doi:10.1002/med.21753 · Cited by 177 · see citing works
Bauer, I., Grozio, A., Lasigliè, D., Basile, G., Sturla, L., Magnone, M., Sociali, G., Soncini, D., Caffa, I., Poggi, A. D., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.405837 · Cited by 176 · see citing works
Mammalian single-strand break repair: Mechanisms and links with chromatin
Caldecott, K. W. (2006) · DNA repair · doi:10.1016/j.dnarep.2006.10.006 · Cited by 174 · see citing works
RETRACTED: Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex
Zhang, Q., Wang, S.-Y., Fleuriel, C., Leprince, D., Rocheleau, J. V., Piston, D. W., & Goodman, R. H. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610590104 · Cited by 171 · see citing works
RetractedNAD metabolism and sirtuins: Metabolic regulation of protein deacetylation in stress and toxicity
Yang, T., & Sauve, A. A. (2006) · The AAPS Journal · doi:10.1208/aapsj080472 · Cited by 170 · see citing works
SIRT6 modulates paclitaxel and epirubicin resistance and survival in breast cancer
Khongkow, M., Olmos, Y., Gong, C., Gomes, A., Monteiro, L. J., Yagüe, E., Cavaco, T. B., Khongkow, P., Man, E. P. S., Laohasinnarong, S., et al. (2013) · Carcinogenesis · doi:10.1093/carcin/bgt098 · Cited by 169 · see citing works
Acetylation of Mitochondrial Proteins in the Heart: The Role of SIRT3
Parodi‐Rullán, R. M., Chapa‐Dubocq, X. R., & Javadov, S. A. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01094 · Cited by 168 · see citing works
Investigating the ADP-ribosyltransferase Activity of Sirtuins with NAD Analogues and 32 P-NAD
Du, J., Jiang, H. X., & Lin, H. (2009) · Biochemistry · doi:10.1021/bi802093g · Cited by 166 · see citing works
Chromatin regulation and genome maintenance by mammalian SIRT6
Tennen, R. I., & Chua, K. F. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.07.009 · Cited by 164 · see citing works
Structural Basis for Sirtuin Activity and Inhibition
Yuan, H., & Marmorstein, R. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r112.372300 · Cited by 160 · see citing works
The emerging and diverse roles of sirtuins in cancer: a clinical perspective
Chen, W., Yuan, H., & Su, L. (2013) · OncoTargets and Therapy · doi:10.2147/ott.s37750 · Cited by 163 · see citing works
Sauve, A. A. (2010) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2010.01.021 · Cited by 161 · see citing works
NAD<sup>+</sup>metabolism and oxidative stress: the golden nucleotide on a crown of thorns
Massudi, H., Grant, R., Guillemin, G. J., & Braidy, N. (2012) · Redox Report · doi:10.1179/1351000212y.0000000001 · Cited by 158 · see citing works
Zhang, G., Deng, Y.-J., Xie, Q.-Q., Ren, E., Ma, Z., He, X., Gao, Y., & Kang, X. (2020) · Clinica Chimica Acta · doi:10.1016/j.cca.2020.04.016 · Cited by 157 · see citing works
SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases
Guo, Z., Li, P., Ge, J., & Li, H. (2022) · Aging and Disease · doi:10.14336/ad.2022.0413 · Cited by 160 · see citing works
Calorie restriction and the exercise of chromatinPreprint
Vaquero, A., & Reinberg, D. (2009) · Genes & Development · doi:10.1101/gad.1807009 · Cited by 154 · see citing works
- Authors
- Liszt, G., Ford, E., Kurtev, M., & Guarente, L.
- Affiliations
- Massachusetts Institute of Technology (US)
- Corresponding author
- Guarente, Leonard
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 280
- Issue
- 22
- Pages
- 21313-21320
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2044836637
- Cited by
- 548
- References
- 31
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 12 · 2023: 20 · 2022: 24 · 2021: 35 · 2020: 30 · 2019: 26 · 2018: 34 · 2017: 25 · 2016: 34 · 2015: 35 · 2014: 23 · 2013: 43 · 2012: 30
- FWCI
- 12.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- SIRT6, ADP-ribosyltransferase, mono-ADP-ribosylation, NAD+-dependent deacetylase, nuclear localization, tissue expression, embryonic development, catalytic mechanism
- MeSH terms
- Actins, Adenosine Diphosphate, Adenosine Diphosphate Ribose, Amino Acid Sequence, Animals, Epitopes, Catalysis, Cell Nucleus, Cytoplasm, Dose-Response Relationship, Drug, Microscopy, Fluorescence, Molecular Sequence Data, Phylogeny, Plasmids, Recombinant Fusion Proteins, Recombinant Proteins, Ribose, RNA, RNA, Messenger, Serine, Time Factors, Tissue Distribution, Blotting, Northern, Blotting, Western, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Fluorescent Antibody Technique, Indirect, Catalytic Domain, Gene Silencing, ADP Ribose Transferases, Sirtuins, NIH 3T3 Cells, Green Fluorescent Proteins, Mice, Sirtuin 2
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