Sirtuin 2

NAD-dependent deacetylase sirtuin 2 is an enzyme that in humans is encoded by the SIRT2 gene.^[5][6][7] SIRT2 is an NAD+ (nicotinamide adenine dinucleotide)-dependent deacetylase. Studies of this protein have often been divergent, highlighting the dependence of pleiotropic effects of SIRT2 on cellular context. The natural polyphenol resveratrol is known to exert opposite actions on neural cells according to their normal or cancerous status.^[8] Similar to other sirtuin family members, SIRT2 displays a ubiquitous distribution. SIRT2 is expressed in a wide range of tissues and organs and has been detected particularly in metabolically relevant tissues, including the brain, muscle, liver, testes, pancreas, kidney, and adipose tissue of mice. Of note, SIRT2 expression is much higher in the brain than all other organs studied, particularly in the cortex, striatum, hippocampus, and spinal cord.^[9]

SIRT2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1J8F, 3ZGO, 3ZGV, 4L3O, 4R8M, 4RMG, 4RMH, 4RMI, 4RMJ, 4Y6O, 5DY4, 5D7O, 5DY5, 4Y6L, 4Y6Q, 4X3O, 4X3P, 5D7P, 5D7Q, 5FYQ
Identifiers
Aliases	SIRT2, SIR2, SIR2L, SIR2L2, sirtuin 2
External IDs	OMIM: 604480; MGI: 1927664; HomoloGene: 40823; GeneCards: SIRT2; OMA:SIRT2 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.2 Start 38,878,555 bp[1] End 38,899,862 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 B1 Start 28,466,160 bp[2] End 28,488,086 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in C1 segment muscle of thigh gastrocnemius muscle right frontal lobe Brodmann area 9 anterior cingulate cortex right hemisphere of cerebellum hypothalamus amygdala tibial nerve Top expressed in optic nerve deep cerebellar nuclei globus pallidus median eminence pontine nuclei genital tubercle internal carotid artery lateral geniculate nucleus dorsal tegmental nucleus sciatic nerve More reference expression data BioGPS More reference expression data
Gene ontology Molecular function histone deacetylase binding transcription factor binding metal ion binding protein deacetylase activity zinc ion binding chromatin binding protein binding histone acetyltransferase binding tubulin deacetylase activity NAD-dependent histone deacetylase activity (H4-K16 specific) NAD-dependent protein deacetylase activity histone deacetylase activity ubiquitin binding NAD+ binding beta-tubulin binding NAD+ ADP-ribosyltransferase activity hydrolase activity NAD-dependent histone deacetylase activity Cellular component cytoplasm cytosol membrane microtubule organizing center chromatin silencing complex perinuclear region of cytoplasm paranode region of axon microtubule cytoskeleton nucleus centrosome cell projection myelin sheath glial cell projection Schmidt-Lanterman incisure paranodal junction perikaryon growth cone spindle chromosome lateral loop mitotic spindle meiotic spindle midbody centriole juxtaparanode region of axon telomere nucleolus mitochondrion plasma membrane Biological process cellular response to molecule of bacterial origin positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia cellular response to epinephrine stimulus tubulin deacetylation rDNA heterochromatin assembly phosphatidylinositol 3-kinase signaling cell cycle positive regulation of DNA binding negative regulation of autophagy cellular response to hypoxia negative regulation of cell population proliferation proteasome-mediated ubiquitin-dependent protein catabolic process cellular lipid catabolic process histone H3 deacetylation peptidyl-lysine deacetylation negative regulation of fat cell differentiation regulation of transcription, DNA-templated substantia nigra development negative regulation of protein catabolic process negative regulation of NLRP3 inflammasome complex assembly negative regulation of oligodendrocyte progenitor proliferation regulation of fat cell differentiation transcription, DNA-templated myelination in peripheral nervous system histone H4 deacetylation regulation of myelination innate immune response hepatocyte growth factor receptor signaling pathway positive regulation of proteasomal ubiquitin-dependent protein catabolic process regulation of exit from mitosis cell differentiation protein ADP-ribosylation immune system process cellular response to hepatocyte growth factor stimulus negative regulation of peptidyl-threonine phosphorylation regulation of phosphorylation negative regulation of transcription by RNA polymerase II nervous system development response to redox state protein deacetylation positive regulation of attachment of spindle microtubules to kinetochore meiosis cellular response to caloric restriction ripoptosome assembly involved in necroptotic process negative regulation of transcription from RNA polymerase II promoter in response to hypoxia negative regulation of transcription, DNA-templated negative regulation of defense response to bacterium positive regulation of execution phase of apoptosis protein kinase B signaling negative regulation of striated muscle tissue development positive regulation of oocyte maturation regulation of cell cycle cell division autophagy positive regulation of meiotic nuclear division cellular response to oxidative stress negative regulation of reactive oxygen species metabolic process histone deacetylation positive regulation of cell division positive regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 22933 64383 Ensembl ENSG00000283100 ENSG00000068903 ENSMUSG00000015149 UniProt Q8IXJ6 Q8VDQ8 RefSeq (mRNA) NM_001193286 NM_012237 NM_030593 NM_001122765 NM_001122766 NM_022432 RefSeq (protein) NP_001180215 NP_036369 NP_085096 NP_001116237 NP_001116238 NP_071877 Location (UCSC) Chr 19: 38.88 – 38.9 Mb Chr 7: 28.47 – 28.49 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Function

Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity.^[7] Cytosolic functions of SIRT2 include the regulation of microtubule acetylation, control of myelination in the central and peripheral nervous system^{[citation needed]} and gluconeogenesis.^[10] There is growing evidence for additional functions of SIRT2 in the nucleus. During the G2/M transition, nuclear SIRT2 is responsible for global deacetylation of H4K16, facilitating H4K20 methylation and subsequent chromatin compaction.^[11] In response to DNA damage, SIRT2 was also found to deacetylate H3K56 in vivo.^[12] Finally, SIRT2 negatively regulates the acetyltransferase activity of the transcriptional co-activator p300 via deacetylation of an automodification loop within its catalytic domain.^[13]

Structure

Gene

Human SIRT2 gene has 18 exons resides on chromosome 19 at q13.^[7] For SIRT2, four different human splice variants are deposited in the GenBank sequence database.^[14]

Protein

SIRT2 gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The protein encoded by this gene is included in class I of the sirtuin family. Several transcript variants are resulted from alternative splicing of this gene.^[7] Only transcript variants 1 and 2 have confirmed protein products of physiological relevance. A leucine-rich nuclear export signal (NES) within the N-terminal region of these two isoforms is identified.^[14] Since deletion of the NES led to nucleocytoplasmic distribution, it is suggested to mediate their cytosolic localization.^[15]

Selective ligands

Inhibitors

• (S)-2-Pentyl-6-chloro,8-bromo-chroman-4-one: IC₅₀ of 1.5 μM, highly selective over SIRT2 and SIRT3^[16]
• 3′-Phenethyloxy-2-anilinobenzamide (33i): IC₅₀ of 0.57 μM^[17]
• AGK2 (C₂₃H₁₃C_l2N₃O₂; 2-cyano-3-[5-(2,5-dichlorophenyl)-2-furanyl]-N-5-quinolinyl-2-propenamide) is a potent, cell-permeable, selective SIRT2 inhibitor that minimally affects both SIRT1 and SIRT3^[18]

Animal studies

Metabolic actions

SIRT2 suppresses inflammatory responses in mice through p65 deacetylation and inhibition of NF-κB activity.^[19] SIRT2 is responsible for the deacetylation and activation of G6PD, stimulating pentose phosphate pathway to supply cytosolic NADPH to counteract oxidative damage and protect mouse erythrocytes.^[20]

Neurodegeneration

Several studies in cell and invertebrate models of Parkinson's disease (PD) and Huntington's disease (HD) suggested potential neuroprotective effects of SIRT2 inhibition, in striking contrast with other sirtuin family members.^[21][22] In addition, recent evidence shows that inhibition of SIRT2 protects against MPTP-induced neuronal loss in vivo.^[23]

Clinical significance

Metabolic actions

Several SIRT2 deacetylation targets play important roles in metabolic homeostasis. SIRT2 inhibits adipogenesis by deacetylating FOXO1 and thus may protect against insulin resistance. SIRT2 sensitizes cells to the action of insulin by physically interacting with and activating Akt and downstream targets. SIRT2 mediates mitochondrial biogenesis by deacetylating PGC-1α, upregulates antioxidant enzyme expression by deacetylating FOXO3a, and thereby reduces ROS levels. Also, Sirt2 can reactivate the inactive G6PD by removing the acetyaltion at K403 ^[24] .

Cell cycle regulation

Although preferentially cytosolic, SIRT2 transiently shuttles to the nucleus during the G2/M transition of the cell cycle, where it has a strong preference for histone H4 lysine 16 (H4K16ac),^[25] thereby regulating chromosomal condensation during mitosis.^[26] During the cell cycle, SIRT2 associates with several mitotic structures including the centrosome, mitotic spindle, and midbody, presumably to ensure normal cell division.^[15] Finally, cells with SIRT2 overexpression exhibit marked prolongation of the cell cycle.^[27]

Tumorigenesis

Mounting evidence implies a role for SIRT2 in tumorigenesis. SIRT2 may suppress or promote tumor growth in a context-dependent manner. SIRT2 has been proposed to act as a tumor suppressor by preventing chromosomal instability during mitosis.^[28] SIRT2-specific inhibitors exhibits broad anticancer activity.^[29][30]

Interactions

SIRT2 has been shown to interact with:

• α-tubulin,^[31]
• TUG,^[32]
• β-catenin,^[33]
• PGAM2,^[34]
• TIAM1,^[35]
• ApoE4,^[36]
• p53,^[37]
• PEPCK,^[38]
• FOXO1,^[39]
• p300,^[40]
• 14-3-3 protein,^[41]
• G6PD,^[20][30][24] and
• CBP.^[42]

References

1. ENSG00000068903 GRCh38: Ensembl release 89: ENSG00000283100, ENSG00000068903 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000015149 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Afshar G, Murnane JP (June 1999). "Characterization of a human gene with sequence homology to Saccharomyces cerevisiae SIR2". Gene. 234 (1): 161–168. doi:10.1016/S0378-1119(99)00162-6. PMID 10393250.
6. Frye RA (June 1999). "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". Biochemical and Biophysical Research Communications. 260 (1): 273–279. doi:10.1006/bbrc.1999.0897. PMID 10381378.
7. "Entrez Gene: SIRT2 sirtuin (silent mating type information regulation 2 homolog) 2 (S. cerevisiae)".
8. Sayd S, Junier MP, Chneiweiss H (May 2014). "[SIRT2, a multi-talented deacetylase]". Médecine/Sciences. 30 (5): 532–536. doi:10.1051/medsci/20143005016. PMID 24939540.
9. Maxwell MM, Tomkinson EM, Nobles J, Wizeman JW, Amore AM, Quinti L, et al. (October 2011). "The Sirtuin 2 microtubule deacetylase is an abundant neuronal protein that accumulates in the aging CNS". Human Molecular Genetics. 20 (20): 3986–3996. doi:10.1093/hmg/ddr326. PMC 3203628. PMID 21791548.
10. North BJ, Marshall BL, Borra MT, Denu JM, Verdin E (February 2003). "The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase". Molecular Cell. 11 (2): 437–444. doi:10.1016/s1097-2765(03)00038-8. PMID 12620231.
11. Serrano L, Martínez-Redondo P, Marazuela-Duque A, Vazquez BN, Dooley SJ, Voigt P, et al. (March 2013). "The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation". Genes & Development. 27 (6): 639–653. doi:10.1101/gad.211342.112. PMC 3613611. PMID 23468428.
12. Vempati RK, Jayani RS, Notani D, Sengupta A, Galande S, Haldar D (September 2010). "p300-mediated acetylation of histone H3 lysine 56 functions in DNA damage response in mammals". The Journal of Biological Chemistry. 285 (37): 28553–28564. doi:10.1074/jbc.M110.149393. PMC 2937881. PMID 20587414.
13. Black JC, Mosley A, Kitada T, Washburn M, Carey M (November 2008). "The SIRT2 deacetylase regulates autoacetylation of p300". Molecular Cell. 32 (3): 449–455. doi:10.1016/j.molcel.2008.09.018. PMC 2645867. PMID 18995842.
14. Rack JG, VanLinden MR, Lutter T, Aasland R, Ziegler M (April 2014). "Constitutive nuclear localization of an alternatively spliced sirtuin-2 isoform". Journal of Molecular Biology. 426 (8): 1677–1691. doi:10.1016/j.jmb.2013.10.027. hdl:1956/10670. PMID 24177535.
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16. Fridén-Saxin M, Seifert T, Landergren MR, Suuronen T, Lahtela-Kakkonen M, Jarho EM, et al. (August 2012). "Synthesis and evaluation of substituted chroman-4-one and chromone derivatives as sirtuin 2-selective inhibitors". Journal of Medicinal Chemistry. 55 (16): 7104–7113. doi:10.1021/jm3005288. PMC 3426190. PMID 22746324.
17. Suzuki T, Khan MN, Sawada H, Imai E, Itoh Y, Yamatsuta K, et al. (June 2012). "Design, synthesis, and biological activity of a novel series of human sirtuin-2-selective inhibitors". Journal of Medicinal Chemistry. 55 (12): 5760–5773. doi:10.1021/jm3002108. PMID 22642300.
18. Wawruszak A, Luszczki J, Czerwonka A, Okon E, Stepulak A (April 2022). "Assessment of Pharmacological Interactions between SIRT2 Inhibitor AGK2 and Paclitaxel in Different Molecular Subtypes of Breast Cancer Cells". Cells. 11 (7): 1211. doi:10.3390/cells11071211. PMC 8998062. PMID 35406775. This article incorporates text from this source, which is available under the CC BY 4.0 license.
19. Gomes P, Fleming Outeiro T, Cavadas C (November 2015). "Emerging Role of Sirtuin 2 in the Regulation of Mammalian Metabolism". Trends in Pharmacological Sciences. 36 (11): 756–768. doi:10.1016/j.tips.2015.08.001. PMID 26538315.
20. Wang YP, Zhou LS, Zhao YZ, Wang SW, Chen LL, Liu LX, et al. (June 2014). "Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress". The EMBO Journal. 33 (12): 1304–1320. doi:10.1002/embj.201387224. PMC 4194121. PMID 24769394.
21. Outeiro TF, Kontopoulos E, Altmann SM, Kufareva I, Strathearn KE, Amore AM, et al. (July 2007). "Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease". Science. 317 (5837): 516–519. Bibcode:2007Sci...317..516O. doi:10.1126/science.1143780. PMID 17588900. S2CID 84493360.
22. Luthi-Carter R, Taylor DM, Pallos J, Lambert E, Amore A, Parker A, et al. (April 2010). "SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis". Proceedings of the National Academy of Sciences of the United States of America. 107 (17): 7927–7932. Bibcode:2010PNAS..107.7927L. doi:10.1073/pnas.1002924107. PMC 2867924. PMID 20378838.
23. Chen X, Wales P, Quinti L, Zuo F, Moniot S, Herisson F, et al. (2015). "The sirtuin-2 inhibitor AK7 is neuroprotective in models of Parkinson's disease but not amyotrophic lateral sclerosis and cerebral ischemia". PLOS ONE. 10 (1): e0116919. Bibcode:2015PLoSO..1016919C. doi:10.1371/journal.pone.0116919. PMC 4301865. PMID 25608039.
24. Wu F, Muskat NH, Dvilansky I, Koren O, Shahar A, Gazit R, et al. (October 2023). "Acetylation-dependent coupling between G6PD activity and apoptotic signaling". Nature Communications. 14 (1): 6208. doi:10.1038/s41467-023-41895-2. PMC 10556143. PMID 37798264.
25. Vaquero A, Scher MB, Lee DH, Sutton A, Cheng HL, Alt FW, et al. (May 2006). "SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis". Genes & Development. 20 (10): 1256–1261. doi:10.1101/gad.1412706. PMC 1472900. PMID 16648462.
26. Inoue T, Hiratsuka M, Osaki M, Yamada H, Kishimoto I, Yamaguchi S, et al. (February 2007). "SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress". Oncogene. 26 (7): 945–957. doi:10.1038/sj.onc.1209857. PMID 16909107. S2CID 21357335.
27. Dryden SC, Nahhas FA, Nowak JE, Goustin AS, Tainsky MA (May 2003). "Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle". Molecular and Cellular Biology. 23 (9): 3173–3185. doi:10.1128/mcb.23.9.3173-3185.2003. PMC 153197. PMID 12697818.
28. Kim HS, Vassilopoulos A, Wang RH, Lahusen T, Xiao Z, Xu X, et al. (October 2011). "SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity". Cancer Cell. 20 (4): 487–499. doi:10.1016/j.ccr.2011.09.004. PMC 3199577. PMID 22014574.
29. Jing H, Hu J, He B, Negrón Abril YL, Stupinski J, Weiser K, et al. (March 2016). "A SIRT2-Selective Inhibitor Promotes c-Myc Oncoprotein Degradation and Exhibits Broad Anticancer Activity". Cancer Cell. 29 (3): 297–310. doi:10.1016/j.ccell.2016.02.007. PMC 4811675. PMID 26977881.
30. Xu SN, Wang TS, Li X, Wang YP (September 2016). "SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation". Scientific Reports. 6: 32734. Bibcode:2016NatSR...632734X. doi:10.1038/srep32734. PMC 5009355. PMID 27586085.
31. Yuan Q, Zhan L, Zhou QY, Zhang LL, Chen XM, Hu XM, et al. (October 2015). "SIRT2 regulates microtubule stabilization in diabetic cardiomyopathy". European Journal of Pharmacology. 764: 554–561. doi:10.1016/j.ejphar.2015.07.045. PMID 26209361.
32. Belman JP, Bian RR, Habtemichael EN, Li DT, Jurczak MJ, Alcázar-Román A, et al. (February 2015). "Acetylation of TUG protein promotes the accumulation of GLUT4 glucose transporters in an insulin-responsive intracellular compartment". The Journal of Biological Chemistry. 290 (7): 4447–4463. doi:10.1074/jbc.M114.603977. PMC 4326849. PMID 25561724.
33. Nguyen P, Lee S, Lorang-Leins D, Trepel J, Smart DK (September 2014). "SIRT2 interacts with β-catenin to inhibit Wnt signaling output in response to radiation-induced stress". Molecular Cancer Research. 12 (9): 1244–1253. doi:10.1158/1541-7786.MCR-14-0223-T. PMC 4163538. PMID 24866770.
34. Xu Y, Li F, Lv L, Li T, Zhou X, Deng CX, et al. (July 2014). "Oxidative stress activates SIRT2 to deacetylate and stimulate phosphoglycerate mutase". Cancer Research. 74 (13): 3630–3642. doi:10.1158/0008-5472.CAN-13-3615. PMC 4303242. PMID 24786789.
35. Saxena M, Dykes SS, Malyarchuk S, Wang AE, Cardelli JA, Pruitt K (January 2015). "The sirtuins promote Dishevelled-1 scaffolding of TIAM1, Rac activation and cell migration". Oncogene. 34 (2): 188–198. doi:10.1038/onc.2013.549. PMC 4067478. PMID 24362520.
36. Theendakara V, Patent A, Peters Libeu CA, Philpot B, Flores S, Descamps O, et al. (November 2013). "Neuroprotective Sirtuin ratio reversed by ApoE4". Proceedings of the National Academy of Sciences of the United States of America. 110 (45): 18303–18308. Bibcode:2013PNAS..11018303T. doi:10.1073/pnas.1314145110. PMC 3831497. PMID 24145446.
37. van Leeuwen IM, Higgins M, Campbell J, McCarthy AR, Sachweh MC, Navarro AM, et al. (April 2013). "Modulation of p53 C-terminal acetylation by mdm2, p14ARF, and cytoplasmic SirT2". Molecular Cancer Therapeutics. 12 (4): 471–480. doi:10.1158/1535-7163.MCT-12-0904. PMID 23416275.
38. Jiang W, Wang S, Xiao M, Lin Y, Zhou L, Lei Q, et al. (July 2011). "Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase". Molecular Cell. 43 (1): 33–44. doi:10.1016/j.molcel.2011.04.028. PMC 3962309. PMID 21726808.
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42. Shimazu T, Horinouchi S, Yoshida M (February 2007). "Multiple histone deacetylases and the CREB-binding protein regulate pre-mRNA 3'-end processing". The Journal of Biological Chemistry. 282 (7): 4470–4478. doi:10.1074/jbc.M609745200. PMID 17172643.

Further reading

• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–113. doi:10.1006/abio.1996.0138. PMID 8619474.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, et al. (April 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–358. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Frye RA (July 2000). "Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins". Biochemical and Biophysical Research Communications. 273 (2): 793–798. doi:10.1006/bbrc.2000.3000. PMID 10873683.
• Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, et al. (August 2000). "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning". Proceedings of the National Academy of Sciences of the United States of America. 97 (17): 9543–9548. Bibcode:2000PNAS...97.9543H. doi:10.1073/pnas.160270997. PMC 16901. PMID 10931946.
• Finnin MS, Donigian JR, Pavletich NP (July 2001). "Structure of the histone deacetylase SIRT2". Nature Structural Biology. 8 (7): 621–625. doi:10.1038/89668. PMID 11427894. S2CID 27800665.
• Grozinger CM, Chao ED, Blackwell HE, Moazed D, Schreiber SL (October 2001). "Identification of a class of small molecule inhibitors of the sirtuin family of NAD-dependent deacetylases by phenotypic screening". The Journal of Biological Chemistry. 276 (42): 38837–38843. doi:10.1074/jbc.M106779200. PMID 11483616.
• Borra MT, O'Neill FJ, Jackson MD, Marshall B, Verdin E, Foltz KR, et al. (April 2002). "Conserved enzymatic production and biological effect of O-acetyl-ADP-ribose by silent information regulator 2-like NAD+-dependent deacetylases". The Journal of Biological Chemistry. 277 (15): 12632–12641. doi:10.1074/jbc.M111830200. PMID 11812793.
• De Smet C, Nishimori H, Furnari FB, Bögler O, Huang HJ, Cavenee WK (May 2002). "A novel seven transmembrane receptor induced during the early steps of astrocyte differentiation identified by differential expression". Journal of Neurochemistry. 81 (3): 575–588. doi:10.1046/j.1471-4159.2002.00847.x. PMID 12065666. S2CID 23925334.
• North BJ, Marshall BL, Borra MT, Denu JM, Verdin E (February 2003). "The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase". Molecular Cell. 11 (2): 437–444. doi:10.1016/S1097-2765(03)00038-8. PMID 12620231.
• Dryden SC, Nahhas FA, Nowak JE, Goustin AS, Tainsky MA (May 2003). "Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle". Molecular and Cellular Biology. 23 (9): 3173–3185. doi:10.1128/MCB.23.9.3173-3185.2003. PMC 153197. PMID 12697818.
• Fulco M, Schiltz RL, Iezzi S, King MT, Zhao P, Kashiwaya Y, et al. (July 2003). "Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state". Molecular Cell. 12 (1): 51–62. doi:10.1016/S1097-2765(03)00226-0. PMID 12887892.
• Hiratsuka M, Inoue T, Toda T, Kimura N, Shirayoshi Y, Kamitani H, et al. (September 2003). "Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene". Biochemical and Biophysical Research Communications. 309 (3): 558–566. doi:10.1016/j.bbrc.2003.08.029. PMID 12963026.
• van der Horst A, Tertoolen LG, de Vries-Smits LM, Frye RA, Medema RH, Burgering BM (July 2004). "FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1)". The Journal of Biological Chemistry. 279 (28): 28873–28879. doi:10.1074/jbc.M401138200. PMID 15126506.
• Bae NS, Swanson MJ, Vassilev A, Howard BH (June 2004). "Human histone deacetylase SIRT2 interacts with the homeobox transcription factor HOXA10". Journal of Biochemistry. 135 (6): 695–700. doi:10.1093/jb/mvh084. PMID 15213244.
• de Oliveira RM, Sarkander J, Kazantsev AG, Outeiro TF (2012). "SIRT2 as a Therapeutic Target for Age-Related Disorders". Frontiers in Pharmacology. 3: 82. doi:10.3389/fphar.2012.00082. PMC 3342661. PMID 22563317.

External links

• Overview of all the structural information available in the PDB for UniProt: Q8IXJ6 (NAD-dependent protein deacetylase sirtuin-2) at the PDBe-KB.