请输入您要查询的百科知识：

　

词条 Sirtuin 1
释义

  1. Function

  2. Selective ligands

      Activators  

  3. Interactions

  4. Sir2

     Method of action and observed effects 

  5. Activation of SIRT1 in mice

  6. Homologous recombination

  7. References

  8. Further reading

  9. External links

{{Infobox_gene}}Sirtuin 1, also known as NAD-dependent deacetylase sirtuin-1, is a protein that in humans is encoded by the SIRT1 gene.[1][2][3]

SIRT1 stands for sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae), referring to the fact that its sirtuin homolog (biological equivalent across species) in yeast (S. cerevisiae) is Sir2. SIRT1 is an enzyme that deacetylates proteins that contribute to cellular regulation (reaction to stressors, longevity).[4]

Function

Sirtuin 1 is a member of the sirtuin family of proteins, homologs of the Sir2 gene in S. cerevisiae. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family.[2]

Sirtuin 1 is downregulated in cells that have high insulin resistance and inducing its expression increases insulin sensitivity, suggesting the molecule is associated with improving insulin sensitivity.[6] Furthermore, SIRT1 was shown to de-acetylate and affect the activity of both members of the PGC1-alpha/ERR-alpha complex, which are essential metabolic regulatory transcription factors.[5][6][7][8][9][10]

In mammals, SIRT1 has been shown to deacetylate and thereby deactivate the p53 protein.[11] SIRT1 also stimulates autophagy by preventing acetylation of proteins (via deacetylation) required for autophagy as demonstrated in cultured cells and embryonic and neonatal tissues. This function provides a link between sirtuin expression and the cellular response to limited nutrients due to caloric restriction.[12] Furthermore, SIRT1 was shown to de-acetylate and affect the activity of both members of the PGC1-alpha/ERR-alpha complex, which are essential metabolic regulatory transcription factors.[5][6][7][8][9][10]

Human aging is characterized by a chronic, low-grade inflammation level[13] and NF-κB is the main transcriptional regulator of genes related to inflammation.[14] SIRT1 inhibits NF-κB-regulated gene expression by deacetylating the RelA/p65 subunit of NF-κB at lysine 310.[15][16]

SIRT1 plays a role in activating T helper 17 cells, which contribute to autoimmune disease; efforts to activate SIRT1 therapeutically may trigger or exacerbate autoimmune disease.[17]

Selective ligands

Activators

  • Lamin A is a protein that had been identified as a direct activator of Sirtuin 1 during a study on progeria.[18]
  • Resveratrol has been claimed to be an activator of Sirtuin 1,[19] but this effect has been disputed based on the fact that the initially used activity assay, using a non-physiological substrate peptide, can produce artificial results.[20][21] Resveratrol increases the expression of SIRT1, meaning that it does increase the activity of SIRT1, though not necessarily by direct activation.[22] However, resveratrol was later shown to directly activate Sirtuin 1 against non-modified peptide substrates.[23][24] Resveratrol also enhances the binding between Sirtuin 1 and Lamin A.[18] In addition to resveratrol, a range of other plant-derived polyphenols have also been shown to interact with SIRT1.[25]
  • SRT-1720 was also claimed to be an activator,[19] but this now has been questioned.[26]
  • Methylene blue [27] by increasing NAD+/NADH ratio.
  • Metformin activates both PRKA and SIRT1.[28]

Interactions

Sirtuin 1 has been shown to interact with HEY2,[29] PGC1-alpha,[7] ERR-alpha,[5] and AIRE.[30] Mir-132 microRNA has been reported to interact with Sirtuin 1 mRNA, so as to reduce protein expression. This has been linked to insulin resistance in the obese.[31]

Human Sirt1 has been reported having 136 direct interactions in Interactomic studies involved in numerous processes.[32]

Sir2

Sir2 (whose homolog in mammals is known as SIRT1) was the first gene of the sirtuin genes to be found. It was found in budding yeast, and, since then, members of this highly conserved family have been found in nearly all organisms studied.[33] Sirtuins are hypothesized to play a key role in an organism's response to stresses (such as heat or starvation) and to be responsible for the lifespan-extending effects of calorie restriction.[34][35]

The three letter yeast gene symbol Sir stands for Silent Information Regulator while the number 2 is representative of the fact that it was the second SIR gene discovered and characterized.[36][37]

In the roundworm, Caenorhabditis elegans, Sir-2.1 is used to denote the gene product most similar to yeast Sir2 in structure and activity.[38][39]

Method of action and observed effects

Sirtuins act primarily by removing acetyl groups from lysine residues within proteins in the presence of NAD+; thus, they are classified as "NAD+-dependent deacetylases" and have EC number 3.5.1.[40] They add the acetyl group from the protein to the ADP-ribose component of NAD+ to form O-acetyl-ADP-ribose. The HDAC activity of Sir2 results in tighter packaging of chromatin and a reduction in transcription at the targeted gene locus. The silencing activity of Sir2 is most prominent at telomeric sequences, the hidden MAT loci (HM loci), and the ribosomal DNA (rDNA) locus (RDN1) from which ribosomal RNA is transcribed.

Limited overexpression of the Sir2 gene results in a lifespan extension of about 30%,[41] if the lifespan is measured as the number of cell divisions the mother cell can undergo before cell death. Concordantly, deletion of Sir2 results in a 50% reduction in lifespan.[41] In particular, the silencing activity of Sir2, in complex with Sir3 and Sir4, at the HM loci prevents simultaneous expression of both mating factors which can cause sterility and shortened lifespan.[42] Additionally, Sir2 activity at the rDNA locus is correlated with a decrease in the formation of rDNA circles. Chromatin silencing, as a result of Sir2 activity, reduces homologous recombination between rDNA repeats, which is the process leading to the formation of rDNA circles. As accumulation of these rDNA circles is the primary way in which yeast are believed to "age", then the action of Sir2 in preventing accumulation of these rDNA circles is a necessary factor in yeast longevity.[42]

Starving of yeast cells leads to a similarly extended lifespan, and indeed starving increases the available amount of NAD+ and reduces nicotinamide, both of which have the potential to increase the activity of Sir2. Furthermore, removing the Sir2 gene eliminates the life-extending effect of caloric restriction.[43] Experiments in the nematode Caenorhabditis elegans and in the fruit fly Drosophila melanogaster[44] support these findings. {{As of|2006}}, experiments in mice are underway.[34]

However, some other findings call the above interpretation into question. If one measures the lifespan of a yeast cell as the amount of time it can live in a non-dividing stage, then silencing the Sir2 gene actually increases lifespan [45] Furthermore, calorie restriction can substantially prolong reproductive lifespan in yeast even in the absence of Sir2.[46]

In organisms more complicated than yeast, it appears that Sir2 acts by deacetylation of several other proteins besides histones.

Resveratrol is a substance that has been shown through experiment to have a number of life-extending and health benefits in various species; it also increases the activity of Sir2, which is the postulated reason for its beneficial effects. Resveratrol is produced by plants when they are stressed, and it is possible that plants use the substance to increase their own Sir2 activity in order to survive periods of stress.[34] Although there is mounting evidence for this hypothesis, its validity is debated.[26][20][47][21]

In the fruit fly Drosophilia melanogaster, the Sir2 gene does not seem to be essential; loss of a sirtuin gene has only very subtle effects.[43] However, mice lacking the SIRT1 gene (the sir2 biological equivalent) were smaller than normal at birth, often died early or became sterile.[48]

Activation of SIRT1 in mice

Increased expression of SIRT1 protein, when induced by a synthetic small molecule activator of SIRT1 (SRT2104), extended both the mean and maximal lifespan of mice.[49] In these mice health was also improved as well as bone and muscle mass. Another SIRT1 activator (SRT1720) also extended lifespan and improved the health of mice.[50]

Homologous recombination

SIRT1 protein actively promotes homologous recombination (HR) in human cells, and likely promotes recombinational repair of DNA breaks.[51] SIRT1 mediated HR requires the WRN protein.[51] WRN protein functions in double-strand break repair by HR.[52] WRN protein is a RecQ helicase, and in its mutated form gives rise to Werner syndrome, a genetic condition in humans characterized by numerous features of premature aging. These findings link SIRT1 function to HR, a DNA repair process that is likely necessary for maintaining the integrity of the genome during aging.[51]

References

1. ^{{cite journal | vauthors = Frye RA | title = 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 | journal = Biochemical and Biophysical Research Communications | volume = 260 | issue = 1 | pages = 273–79 | date = June 1999 | pmid = 10381378 | doi = 10.1006/bbrc.1999.0897 }}
2. ^1 {{cite web | title = Entrez Gene: SIRT1 sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23411| accessdate = }}
3. ^{{UCSC genome browser|SIRT1}}
4. ^{{cite journal | vauthors = Sinclair DA, Guarente L | title = Unlocking the Secrets of Longevity Genes | journal = Scientific American | volume = 294| issue = 3| pages = 48–51, 54–7|date=March 2006 | pmid = 16502611| doi = 10.1038/scientificamerican0306-48| bibcode = 2006SciAm.294c..48S }}
5. ^1 2 {{cite journal | vauthors = Wilson BJ, Tremblay AM, Deblois G, Sylvain-Drolet G, Giguère V | title = An acetylation switch modulates the transcriptional activity of estrogen-related receptor alpha | journal = Molecular Endocrinology | volume = 24 | issue = 7 | pages = 1349–58 | date = July 2010 | pmid = 20484414 | pmc = 5417470 | doi = 10.1210/me.2009-0441 }}
6. ^1 {{cite journal | vauthors = Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P | title = Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1 | journal = Nature | volume = 434 | issue = 7029 | pages = 113–8 | date = March 2005 | pmid = 15744310 | doi = 10.1038/nature03354 | bibcode = 2005Natur.434..113R }}
7. ^1 2 {{cite journal | vauthors = Nemoto S, Fergusson MM, Finkel T | title = SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1{alpha} | journal = The Journal of Biological Chemistry | volume = 280 | issue = 16 | pages = 16456–60 | date = April 2005 | pmid = 15716268 | doi = 10.1074/jbc.M501485200 }}
8. ^1 {{cite journal | vauthors = Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J | title = Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha | journal = Cell | volume = 127 | issue = 6 | pages = 1109–22 | date = December 2006 | pmid = 17112576 | doi = 10.1016/j.cell.2006.11.013 }}
9. ^1 {{cite journal | vauthors = Liu Y, Dentin R, Chen D, Hedrick S, Ravnskjaer K, Schenk S, Milne J, Meyers DJ, Cole P, Yates J, Olefsky J, Guarente L, Montminy M | title = A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange | journal = Nature | volume = 456 | issue = 7219 | pages = 269–73 | date = November 2008 | pmid = 18849969 | pmc = 2597669 | doi = 10.1038/nature07349 | bibcode = 2008Natur.456..269L }}
10. ^1 {{cite journal | vauthors = Cantó C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, Elliott PJ, Puigserver P, Auwerx J | title = AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity | journal = Nature | volume = 458 | issue = 7241 | pages = 1056–60 | date = April 2009 | pmid = 19262508 | pmc = 3616311 | doi = 10.1038/nature07813 | bibcode = 2009Natur.458.1056C }}
11. ^{{EntrezGene|23411}} Human Sirt1
12. ^{{cite journal | vauthors = Lee IH, Cao L, Mostoslavsky R, Lombard DB, Liu J, Bruns NE, Tsokos M, Alt FW, Finkel T | title = A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 9 | pages = 3374–89 | date = March 2008 | pmid = 18296641 | doi = 10.1073/pnas.0712145105 | pmc=2265142| bibcode = 2008PNAS..105.3374L }}
13. ^{{cite journal | vauthors = Franceschi C, Campisi J | title = Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases | journal = The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences | volume = 69 | issue = S1 | pages = S4–S9 | date = June 2014 | pmid = 24833586 | doi = 10.1093/gerona/glu057 }}
14. ^{{cite journal | vauthors = Lawrence T | title = The nuclear factor NF-kappaB pathway in inflammation | journal = Cold Spring Harbor Perspectives in Biology | volume = 1 | issue = 6 | page = a001651 | date = December 2009 | pmid =20457564 | doi = 10.1101/cshperspect.a001651 | pmc=2882124}}
15. ^{{cite journal | vauthors = Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW | title = Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase | journal = The EMBO Journal | volume = 23 | issue = 12 | pages = 2369–80 | date = June 2004 | pmid = 15152190 | doi = 10.1038/sj.emboj.7600244 | pmc=423286}}
16. ^{{cite journal | vauthors = Kauppinen A, Suuronen T, Ojala J, Kaarniranta K, Salminen A | title = Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders | journal = Cellular Signalling | volume = 25 | issue = 10 | pages = 1939–48 | date = October 2013 | pmid = 23770291 | doi = 10.1016/j.cellsig.2013.06.007 }}
17. ^{{cite journal|last1=Verdin|first1=E|title=NAD⁺ in aging, metabolism, and neurodegeneration|journal=Science |date=4 December 2015|volume=350|issue=6265|pages=1208–13|doi=10.1126/science.aac4854|pmid=26785480|bibcode=2015Sci...350.1208V}}
18. ^1 {{cite journal | vauthors = Liu B, Ghosh S, Yang X, Zheng H, Liu X, Wang Z, Jin G, Zheng B, Kennedy BK, Suh Y, Kaeberlein M, Tryggvason K, Zhou Z | title = Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria | journal = Cell Metabolism | volume = 16 | issue = 6 | pages = 738–50 | date = December 2012 | pmid = 23217256 | pmc = | doi = 10.1016/j.cmet.2012.11.007 }}
19. ^1 {{cite journal | vauthors = Alcaín FJ, Villalba JM | title = Sirtuin activators | journal = Expert Opinion on Therapeutic Patents | volume = 19 | issue = 4 | pages = 403–14 | date = April 2009 | pmid = 19441923 | doi = 10.1517/13543770902762893 }}
20. ^1 {{cite journal | vauthors = Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell SD, Napper A, Curtis R, DiStefano PS, Fields S, Bedalov A, Kennedy BK | title = Substrate-specific activation of sirtuins by resveratrol | journal = The Journal of Biological Chemistry | volume = 280 | issue = 17 | pages = 17038–45 | date = April 2005 | pmid = 15684413 | doi = 10.1074/jbc.M500655200 }}
21. ^1 {{cite journal | vauthors = Beher D, Wu J, Cumine S, Kim KW, Lu SC, Atangan L, Wang M | title = Resveratrol is not a direct activator of SIRT1 enzyme activity | journal = Chemical Biology & Drug Design | volume = 74 | issue = 6 | pages = 619–24 | date = December 2009 | pmid = 19843076 | doi = 10.1111/j.1747-0285.2009.00901.x }}
22. ^1 {{cite journal | vauthors = Sun C, Zhang F, Ge X, Yan T, Chen X, Shi X, Zhai Q | title = SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B | journal = Cell Metabolism | volume = 6 | issue = 4 | pages = 307–19 | date = October 2007 | pmid = 17908559 | doi = 10.1016/j.cmet.2007.08.014 }}
23. ^{{cite journal | vauthors = Lakshminarasimhan M, Rauh D, Schutkowski M, Steegborn C | title = Sirt1 activation by resveratrol is substrate sequence-selective | journal = Aging | volume = 5 | issue = 3 | pages = 151–54 | date = March 2013 | pmid = 23524286 | doi = 10.18632/aging.100542 | pmc=3629287}}
24. ^{{cite journal | vauthors = Hubbard BP, Gomes AP, Dai H, Li J, Case AW, Considine T, Riera TV, Lee JE, E SY, Lamming DW, Pentelute BL, Schuman ER, Stevens LA, Ling AJ, Armour SM, Michan S, Zhao H, Jiang Y, Sweitzer SM, Blum CA, Disch JS, Ng PY, Howitz KT, Rolo AP, Hamuro Y, Moss J, Perni RB, Ellis JL, Vlasuk GP, Sinclair DA | title = Evidence for a common mechanism of SIRT1 regulation by allosteric activators | journal = Science | volume = 339 | issue = 6124 | pages = 1216–19 | date = March 2013 | pmid = 23471411 | doi = 10.1126/science.1231097 | pmc=3799917| bibcode = 2013Sci...339.1216H }}
25. ^{{cite journal | vauthors = Ajami M, Pazoki-Toroudi H, Amani H, Nabavi SF, Braidy N, Vacca RA, Atanasov AG, Mocan A, Nabavi SM | title = Therapeutic role of sirtuins in neurodegenerative disease and their modulation by polyphenols | journal = Neuroscience and Biobehavioral Reviews | volume = 73 | issue = | pages = 39–47 | date = November 2016 | pmid = 27914941 | doi = 10.1016/j.neubiorev.2016.11.022 }}
26. ^1 {{cite journal | vauthors = Pacholec M, Bleasdale JE, Chrunyk B, Cunningham D, Flynn D, Garofalo RS, Griffith D, Griffor M, Loulakis P, Pabst B, Qiu X, Stockman B, Thanabal V, Varghese A, Ward J, Withka J, Ahn K | title = SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1 | journal = The Journal of Biological Chemistry | volume = 285 | issue = 11 | pages = 8340–51 | date = March 2010 | pmid = 20061378 | pmc = 2832984 | doi = 10.1074/jbc.M109.088682 }}
27. ^{{cite journal | vauthors = Shin SY, Kim TH, Wu H, Choi YH, Kim SG | title = SIRT1 activation by methylene blue, a repurposed drug, leads to AMPK-mediated inhibition of steatosis and steatohepatitis | journal = European Journal of Pharmacology | volume = 727 | pages = 115–24 | date = March 2014 | pmid = 24486702 | doi = 10.1016/j.ejphar.2014.01.035 }}
28. ^{{cite journal | vauthors = Song YM, Lee YH, Kim JW, Ham DS, Kang ES, Cha BS, Lee HC, Lee BW | title = Metformin alleviates hepatosteatosis by restoring SIRT1-mediated autophagy induction via an AMP-activated protein kinase-independent pathway | journal = Autophagy | volume = 11 | issue = 1 | pages = 46–59 | date = 2015 | pmid = 25484077 | pmc = 4502778 | doi = 10.4161/15548627.2014.984271 }}
29. ^{{cite journal | vauthors = Takata T, Ishikawa F | title = Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression | journal = Biochemical and Biophysical Research Communications | volume = 301 | issue = 1 | pages = 250–57 | date = January 2003 | pmid = 12535671 | doi = 10.1016/S0006-291X(02)03020-6 }}
30. ^{{cite journal | vauthors = Chuprin A, Avin A, Goldfarb Y, Herzig Y, Levi B, Jacob A, Sela A, Katz S, Grossman M, Guyon C, Rathaus M, Cohen HY, Sagi I, Giraud M, McBurney MW, Husebye ES, Abramson J | title = The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance. | journal = Nature Immunology | volume = 16 | issue = 7 | pages = 737–45 | date = July 2015 | pmid = 26006015 | doi = 10.1038/ni.3194 }}
31. ^{{cite journal | vauthors = Strum JC, Johnson JH, Ward J, Xie H, Feild J, Hester A, Alford A, Waters KM | title = MicroRNA 132 regulates nutritional stress-induced chemokine production through repression of SirT1 | journal = Molecular Endocrinology | volume = 23 | issue = 11 | pages = 1876–84 | date = November 2009 | pmid = 19819989 | pmc = 5419165 | doi = 10.1210/me.2009-0117 }}
32. ^{{cite journal | vauthors = Sharma A, Gautam V, Costantini S, Paladino A, Colonna G | title = Interactomic and pharmacological insights on human sirt-1 | journal = Frontiers in Pharmacology | volume = 3 | issue = | pages = 40 | year = 2012 | pmid = 22470339 | pmc = 3311038 | doi = 10.3389/fphar.2012.00040 }}
33. ^{{cite journal | vauthors = Frye RA | title = Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins | journal = Biochemical and Biophysical Research Communications | volume = 273 | issue = 2 | pages = 793–98 | date = July 2000 | pmid = 10873683 | doi = 10.1006/bbrc.2000.3000 }}
34. ^1 2 {{cite journal | vauthors = Sinclair DA, Guarente L | title = Unlocking the secrets of longevity genes | journal = Scientific American | volume = 294 | issue = 3 | pages = 48–51, 54–57 | date = March 2006 | pmid = 16502611 | doi = 10.1038/scientificamerican0306-48 | bibcode = 2006SciAm.294c..48S }}
35. ^{{cite journal | vauthors = Noriega LG, Feige JN, Canto C, Yamamoto H, Yu J, Herman MA, Mataki C, Kahn BB, Auwerx J | title = CREB and ChREBP oppositely regulate SIRT1 expression in response to energy availability | journal = EMBO Reports | volume = 12 | issue = 10 | pages = 1069–76 | date = September 2011 | pmid = 21836635 | pmc = 3185337 | doi = 10.1038/embor.2011.151 }}
36. ^{{cite journal | vauthors = Rine J, Herskowitz I | title = Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae | journal = Genetics | volume = 116 | issue = 1 | pages = 9–22 | date = May 1987 | pmid = 3297920 | pmc = 1203125 | url = http://www.genetics.org/cgi/pmidlookup?view=long&pmid=3297920 }}
37. ^{{cite journal | vauthors = North BJ, Verdin E | title = Sirtuins: Sir2-related NAD-dependent protein deacetylases | journal = Genome Biology | volume = 5 | issue = 5 | page = 224 | year = 2004 | pmid = 15128440 | pmc = 416462 | doi = 10.1186/gb-2004-5-5-224 }}
38. ^WormBase Protein Summary: Sir-2.1
39. ^http://mediwire.skyscape.com/main/Default.aspx?P=Content&ArticleID=174239 {{webarchive |url=https://web.archive.org/web/20070927185656/http://mediwire.skyscape.com/main/Default.aspx?P=Content&ArticleID=174239 |date=September 27, 2007 }} Skyscape Content: Do antiaging approaches promote longevity?
40. ^The Sir2 protein family from EMBL's InterPro database
41. ^1 {{cite journal | vauthors = Chang KT, Min KT | title = Regulation of lifespan by histone deacetylase | journal = Ageing Research Reviews | volume = 1 | issue = 3 | pages = 313–26 | date = June 2002 | pmid = 12067588 | doi = 10.1016/S1568-1637(02)00003-X }}
42. ^1 {{cite journal | vauthors = Kaeberlein M, McVey M, Guarente L | title = The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms | journal = Genes & Development | volume = 13 | issue = 19 | pages = 2570–80 | date = October 1999 | pmid = 10521401 | pmc = 317077 | doi = 10.1101/gad.13.19.2570 }}
43. ^1 {{EntrezGene|34708}} Drosophilia Sir2
44. ^{{cite journal | vauthors = Rogina B, Helfand SL | title = Sir2 mediates longevity in the fly through a pathway related to calorie restriction | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 45 | pages = 15998–6003 | date = November 2004 | pmid = 15520384 | pmc = 528752 | doi = 10.1073/pnas.0404184101 | bibcode = 2004PNAS..10115998R }}
45. ^{{cite journal | vauthors = Fabrizio P, Gattazzo C, Battistella L, Wei M, Cheng C, McGrew K, Longo VD | title = Sir2 blocks extreme life-span extension | journal = Cell | volume = 123 | issue = 4 | pages = 655–67 | date = November 2005 | pmid = 16286010 | doi = 10.1016/j.cell.2005.08.042 }}
46. ^{{cite journal | vauthors = Kaeberlein M, Kirkland KT, Fields S, Kennedy BK | title = Sir2-independent life span extension by calorie restriction in yeast | journal = PLoS Biology | volume = 2 | issue = 9 | page = E296 | date = September 2004 | pmid = 15328540 | pmc = 514491 | doi = 10.1371/journal.pbio.0020296 }}
47. ^{{cite journal | vauthors = Borra MT, Smith BC, Denu JM | title = Mechanism of human SIRT1 activation by resveratrol | journal = The Journal of Biological Chemistry | volume = 280 | issue = 17 | pages = 17187–95 | date = April 2005 | pmid = 15749705 | doi = 10.1074/jbc.M501250200 }}
48. ^{{cite journal | vauthors = McBurney MW, Yang X, Jardine K, Hixon M, Boekelheide K, Webb JR, Lansdorp PM, Lemieux M | title = The mammalian SIR2alpha protein has a role in embryogenesis and gametogenesis | journal = Molecular and Cellular Biology | volume = 23 | issue = 1 | pages = 38–54 | date = January 2003 | pmid = 12482959 | pmc = 140671 | doi = 10.1128/MCB.23.1.38-54.2003 }}
49. ^{{cite journal |vauthors=Mercken EM, Mitchell SJ, Martin-Montalvo A, Minor RK, Almeida M, Gomes AP, Scheibye-Knudsen M, Palacios HH, Licata JJ, Zhang Y, Becker KG, Khraiwesh H, González-Reyes JA, Villalba JM, Baur JA, Elliott P, Westphal C, Vlasuk GP, Ellis JL, Sinclair DA, Bernier M, de Cabo R |title=SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass |journal=Aging Cell |volume=13 |issue=5 |pages=787–96 |year=2014 |pmid=24931715 |pmc=4172519 |doi=10.1111/acel.12220 |url=}}
50. ^{{cite journal |vauthors=Mitchell SJ, Martin-Montalvo A, Mercken EM, Palacios HH, Ward TM, Abulwerdi G, Minor RK, Vlasuk GP, Ellis JL, Sinclair DA, Dawson J, Allison DB, Zhang Y, Becker KG, Bernier M, de Cabo R |title=The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet |journal=Cell Rep |volume=6 |issue=5 |pages=836–43 |year=2014 |pmid=24582957 |pmc=4010117 |doi=10.1016/j.celrep.2014.01.031 |url=}}
51. ^1 2 {{cite journal |vauthors=Uhl M, Csernok A, Aydin S, Kreienberg R, Wiesmüller L, Gatz SA |title=Role of SIRT1 in homologous recombination |journal=DNA Repair (Amst.) |volume=9 |issue=4 |pages=383–93 |year=2010 |pmid=20097625 |doi=10.1016/j.dnarep.2009.12.020 |url=}}
52. ^{{cite journal |vauthors=Thompson LH, Schild D |title=Recombinational DNA repair and human disease |journal=Mutat. Res. |volume=509 |issue=1–2 |pages=49–78 |year=2002 |pmid=12427531 |doi= 10.1016/s0027-5107(02)00224-5|url=}}

Further reading

{{refbegin|33em}}
  • {{cite journal | vauthors = Frye RA | title = 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 | journal = Biochemical and Biophysical Research Communications | volume = 260 | issue = 1 | pages = 273–79 | date = June 1999 | pmid = 10381378 | doi = 10.1006/bbrc.1999.0897 }}
  • {{cite journal | vauthors = Frye RA | title = Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins | journal = Biochemical and Biophysical Research Communications | volume = 273 | issue = 2 | pages = 793–98 | date = July 2000 | pmid = 10873683 | doi = 10.1006/bbrc.2000.3000 }}
  • {{cite journal | vauthors = Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A | title = Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs | journal = Genome Research | volume = 11 | issue = 3 | pages = 422–35 | date = March 2001 | pmid = 11230166 | pmc = 311072 | doi = 10.1101/gr.GR1547R }}
  • {{cite journal | vauthors = Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L, Gu W | title = Negative control of p53 by Sir2alpha promotes cell survival under stress | journal = Cell | volume = 107 | issue = 2 | pages = 137–48 | date = October 2001 | pmid = 11672522 | doi = 10.1016/S0092-8674(01)00524-4 }}
  • {{cite journal | vauthors = Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, Guarente L, Weinberg RA | title = hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase | journal = Cell | volume = 107 | issue = 2 | pages = 149–59 | date = October 2001 | pmid = 11672523 | doi = 10.1016/S0092-8674(01)00527-X }}
  • {{cite journal | vauthors = Langley E, Pearson M, Faretta M, Bauer UM, Frye RA, Minucci S, Pelicci PG, Kouzarides T | title = Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence | journal = The EMBO Journal | volume = 21 | issue = 10 | pages = 2383–96 | date = May 2002 | pmid = 12006491 | pmc = 126010 | doi = 10.1093/emboj/21.10.2383 }}
  • {{cite journal | vauthors = Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, Sinclair DA | title = Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 47 | pages = 45099–107 | date = November 2002 | pmid = 12297502 | doi = 10.1074/jbc.M205670200 }}
  • {{cite journal | vauthors = Travers H, Spotswood HT, Moss PA, Turner BM | title = Human CD34+ hematopoietic progenitor cells hyperacetylate core histones in response to sodium butyrate, but not trichostatin A | journal = Experimental Cell Research | volume = 280 | issue = 2 | pages = 149–58 | date = November 2002 | pmid = 12413881 | doi = 10.1006/excr.2002.5632 }}
  • {{cite journal | vauthors = Takata T, Ishikawa F | title = Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression | journal = Biochemical and Biophysical Research Communications | volume = 301 | issue = 1 | pages = 250–57 | date = January 2003 | pmid = 12535671 | doi = 10.1016/S0006-291X(02)03020-6 }}
  • {{cite journal | vauthors = Senawong T, Peterson VJ, Avram D, Shepherd DM, Frye RA, Minucci S, Leid M | title = Involvement of the histone deacetylase SIRT1 in chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein 2-mediated transcriptional repression | journal = The Journal of Biological Chemistry | volume = 278 | issue = 44 | pages = 43041–50 | date = October 2003 | pmid = 12930829 | pmc = 2819354 | doi = 10.1074/jbc.M307477200 }}
  • {{cite journal | vauthors = Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA | title = Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan | journal = Nature | volume = 425 | issue = 6954 | pages = 191–96 | date = September 2003 | pmid = 12939617 | doi = 10.1038/nature01960 | bibcode = 2003Natur.425..191H }}
  • {{cite journal | vauthors = Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME | title = Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase | journal = Science | volume = 303 | issue = 5666 | pages = 2011–15 | date = March 2004 | pmid = 14976264 | doi = 10.1126/science.1094637 | bibcode = 2004Sci...303.2011B }}
  • {{cite journal | vauthors = Motta MC, Divecha N, Lemieux M, Kamel C, Chen D, Gu W, Bultsma Y, McBurney M, Guarente L | title = Mammalian SIRT1 represses forkhead transcription factors | journal = Cell | volume = 116 | issue = 4 | pages = 551–63 | date = February 2004 | pmid = 14980222 | doi = 10.1016/S0092-8674(04)00126-6 }}
  • {{cite journal | vauthors = van der Horst A, Tertoolen LG, de Vries-Smits LM, Frye RA, Medema RH, Burgering BM | title = FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1) | journal = The Journal of Biological Chemistry | volume = 279 | issue = 28 | pages = 28873–79 | date = July 2004 | pmid = 15126506 | doi = 10.1074/jbc.M401138200 }}
  • {{cite journal | vauthors = Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW | title = Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase | journal = The EMBO Journal | volume = 23 | issue = 12 | pages = 2369–80 | date = June 2004 | pmid = 15152190 | pmc = 423286 | doi = 10.1038/sj.emboj.7600244 }}
  • {{cite journal | vauthors = Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, Leid M, McBurney MW, Guarente L | title = Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma | journal = Nature | volume = 429 | issue = 6993 | pages = 771–76 | date = June 2004 | pmid = 15175761 | pmc = 2820247 | doi = 10.1038/nature02583 | bibcode = 2004Natur.429..771P }}
  • {{cite journal | vauthors = Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA | title = Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase | journal = Science | volume = 305 | issue = 5682 | pages = 390–92 | date = July 2004 | pmid = 15205477 | doi = 10.1126/science.1099196 | bibcode = 2004Sci...305..390C }}
  • {{cite journal | vauthors = Miyazaki S, Kakutani K, Yurube T, Maeno K, Takada T, Zhang Z, Kurakawa T, Terashima Y, Ito M, Ueha T, Matsushita T, Kuroda R, Kurosaka M, Nishida K | title = Recombinant human SIRT1 protects against nutrient deprivation-induced mitochondrial apoptosis through autophagy induction in human intervertebral disc nucleus pulposus cells | journal = Arthritis Research & Therapy | volume = 17 | page = 253 | date = September 2015 | pmid = 26373839 | doi = 10.1186/s13075-015-0763-6 | pmc=4571076}}
{{refend}}

External links

  • [https://web.archive.org/web/20071202143228/http://www.corante.com/pipeline/archives/2005/11/20/sir2_surprise.php Corante weblog] by Derek Lowe about sir2 and SIRT1 research.
  • {{UCSC genome browser|SIRT1}}
  • {{UCSC gene details|SIRT1}}
{{Carbon-nitrogen non-peptide hydrolases}}{{Enzymes}}{{Portal bar|Molecular and Cellular Biology|border=no}}Sirtuïne#Sir2

3 : EC 3.5.1|Aging-related proteins|Aging-related enzymes
随便看

　

开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。

　

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间：2024/9/23 23:30:26