سيروتين-1

Sirtuin 1
البنى المتاحة
	4I5I, 4IF6, 4IG9, 4KXQ
المحددات
الرمزs	SIRT1; SIR2L1
المحددات الخارجية	OMIM: 604479 MGI: 2135607 هومولوجين: 56556 GeneCards: SIRT1 Gene
طبيعة الجين
الوظيفة الجزيئية	• p53 binding; • transcription corepressor activity; • NAD+ ADP-ribosyltransferase activity; • histone deacetylase activity; • protein binding; • protein C-terminus binding; • NAD-dependent histone deacetylase activity; • deacetylase activity; • protein deacetylase activity; • NAD-dependent protein deacetylase activity; • histone binding; • identical protein binding; • HLH domain binding; • bHLH transcription factor binding; • metal ion binding; • NAD-dependent histone deacetylase activity (H3-K9 specific); • mitogen-activated protein kinase binding; • NAD+ binding;
المكون الخلوي	• nuclear chromatin; • nucleus; • nuclear envelope; • nuclear inner membrane; • nucleoplasm; • chromatin silencing complex; • nuclear euchromatin; • nuclear heterochromatin; • nucleolus; • cytoplasm; • PML body; • rDNA heterochromatin; • ESC/E(Z) complex;
العملية الحيوية	• single strand break repair; • negative regulation of transcription from RNA polymerase II promoter; • chromatin silencing at rDNA; • pyrimidine dimer repair by nucleotide-excision repair; • DNA synthesis involved in DNA repair; • angiogenesis; • ovulation from ovarian follicle; • cellular glucose homeostasis; • positive regulation of protein phosphorylation; • positive regulation of adaptive immune response; • DNA replication; • DNA repair; • chromatin silencing; • establishment of chromatin silencing; • maintenance of chromatin silencing; • methylation-dependent chromatin silencing; • transcription, DNA-dependent; • rRNA processing; • protein ADP-ribosylation; • protein deacetylation; • triglyceride mobilization; • response to DNA damage stimulus; • response to oxidative stress; • spermatogenesis; • regulation of mitotic cell cycle; • muscle organ development; • cell aging; • positive regulation of cell proliferation; • cellular response to starvation; • positive regulation of cholesterol efflux; • regulation of glucose metabolic process; • positive regulation of macroautophagy; • protein ubiquitination; • histone deacetylation; • peptidyl-lysine acetylation; • virus-host interaction; • negative regulation of cell growth; • negative regulation of transforming growth factor beta receptor signaling pathway; • negative regulation of prostaglandin biosynthetic process; • protein destabilization; • positive regulation of chromatin silencing; • negative regulation of TOR signaling cascade; • regulation of endodeoxyribonuclease activity; • negative regulation of NF-kappaB transcription factor activity; • response to insulin stimulus; • regulation of protein import into nucleus, translocation; • regulation of smooth muscle cell apoptotic process; • peptidyl-lysine deacetylation; • cellular triglyceride homeostasis; • regulation of peroxisome proliferator activated receptor signaling pathway; • regulation of cell proliferation; • negative regulation of phosphorylation; • cholesterol homeostasis; • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; • regulation of apoptotic process; • positive regulation of apoptotic process; • negative regulation of apoptotic process; • negative regulation of I-kappaB kinase/NF-kappaB cascade; • proteasomal ubiquitin-dependent protein catabolic process; • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; • negative regulation of sequence-specific DNA binding transcription factor activity; • negative regulation of DNA damage response, signal transduction by p53 class mediator; • positive regulation of MHC class II biosynthetic process; • negative regulation of fat cell differentiation; • positive regulation of DNA repair; • negative regulation of transcription, DNA-dependent; • positive regulation of transcription from RNA polymerase II promoter; • positive regulation of insulin receptor signaling pathway; • white fat cell differentiation; • negative regulation of helicase activity; • negative regulation of protein kinase B signaling cascade; • fatty acid homeostasis; • negative regulation of androgen receptor signaling pathway; • cellular response to hydrogen peroxide; • regulation of bile acid biosynthetic process; • histone H3 deacetylation; • cellular response to tumor necrosis factor; • cellular response to hypoxia; • cellular response to ionizing radiation; • regulation of response to stress; • positive regulation of macrophage apoptotic process; • negative regulation of cAMP-dependent protein kinase activity; • positive regulation of cAMP-dependent protein kinase activity; • negative regulation of cellular response to testosterone stimulus; • negative regulation of peptidyl-lysine acetylation; • negative regulation of cellular senescence; • positive regulation of cellular senescence;
نمط تعبير الرنا
	المزيد من التعبيرات المرجعية
الكروموسومات المتناددة Orthologs

عدِّل

هو يعرف بأنه سيروتين-1 ديكاربوكسيليز مبنى على ناد وهو بروتين يمكن فك شفرته في الآدميين بواسطة جين سيرت-1.^[1]^[2]^[3]

مقالة مفصلة: SIRT1 بروتين يؤخر ظهور الشيخوخة

SIRT1 يشير إلىsirtuin (silent mating type information regulation 2 homolog)(الصمت نوع تنظيم تزاوج المعلومات 2 نظير) 1 ( ساكرومايسيس سيريفيساى)، مشيرا إلى أن لها نظير سيروتين (أي ما يعادل البيولوجية عبر الأنواع) في الخميرة (خميرة س) هو Sir2. SIRT1 هو إنزيم أن deacetylates البروتينات التي تساهم في التنظيم الخلوي (كرد فعل على الضغوط، وطول العمر). ^[4]

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

الوظيفة

سيروتين 1 هو عضو في الأسرة sirtuin من البروتينات، homologs من الجين Sir2 فيساكرومايسيس سيريفيساى. وتتميز أفراد أسرة sirtuin بواسطة a sirtuin core domain and grouped into four classes. لم يتم بعد تحديد وظائف sirtuins في الإنسان، ولكن من المعروف أن بروتينات الخميرة sirtuin لتنظيم جينيةepigenetics إسكات الجينات وقمع إعادة التركيب من rDNA. وتشير الدراسات إلى أن sirtuins في الإنسان قد تعمل البروتينات داخل الخلايا التنظيمية كما هو الحال مع أحادية النشاط ADP-ribosyltransferase. يتم تضمين البروتين المشفرة بواسطة هذا الجين في الصف الأول من أسرة سيروتين.^[2]

Sirtuin 1 ينظم باستمرار الخلايا التي تحتوي على مقاومة عالية الأنسولين وتؤكد قابليتها لزيادة حساسية الأنسولين، مما يوحي بإرتباط جزيء مع تحسين حساسية الأنسولين.^[5] وعلاوة على ذلك، فقد تبين SIRT1 لنزع acetylate وتؤثر على نشاط كل من أعضاء PGC 1alpha / ERR ألفا معقدة، والتي هي عوامل النسخ التنظيمية الأيضية الأساسية.^[6]^[7]^[8]^[9]^[10]^[11]

الروابط الانتقائية

المنشطات

لامين أى هو البروتين الذى تم تحديده باعتباره المنشط المباشر ل Sirtuin 1 خلال دراسة على بروجيريا ^[12]
Resveratrol has been claimed to be an activator of Sirtuin 1,^[13] ولكن هذا تم التشكيك به.^[14]^[15] ريسفيراترول يزيد من التعبير عن SIRT1، وهذا يعني أنه يقوم بزيادة نشاط SIRT1، ولكن ليس بالضرورة عن طريق التفعيل المباشر.^[16] ريسفيراترول يعزز الربط بين Sirtuin 1 ولامين أى.^[12]
SRT1720قد زعم أيضا أنه هو المنشط,^[13] ولكن هذا قد تم التساؤل حوله الآن. ^[17]

التفاعلات

وقد تبين Sirtuin 1 إلى تفاعل مع HEY2، ^[18] PGC1-alpha,^[8] و ERR ألفا ^[6] Mir-132 microRNA has been reported to interact with Sirtuin 1 mRNA,، وذلك للحد من البروتين التعبير. وقد تم ربط هذا إلى مقاومة الأنسولين في السمنة.^[19]

وقد تم الإبلاغ أن Sirt1 في الإنسان يشتمل على وجود 136 من التفاعلات المباشرة في الدراسات Interactome المشاركة في عمليات عديدة.^[20]

References

^ 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". Biochem. Biophys. Res. Commun. 260 (1): 273–9. doi:10.1006/bbrc.1999.0897. PMID 10381378.
^ ^أ ^ب "Entrez Gene: SIRT1 sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae)".
^ قالب:UCSC genome browser
^ Sinclair DA, Guarente L (March 2006). "Unlocking the Secrets of Longevity Genes". Scientific American.
^ Sun C, Zhang F, Ge X; et al. (October 2007). "SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B". Cell Metab. 6 (4): 307–19. doi:10.1016/j.cmet.2007.08.014. PMID 17908559. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
^ ^أ ^ب Wilson BJ, Tremblay AM, Deblois G, Sylvain-Drolet G, Giguère V (Jul 2010). "An acetylation switch modulates the transcriptional activity of estrogen-related receptor alpha". Mol. Endocrinol. 24 (7): 1349–58. doi:10.1210/me.2009-0441. PMID 20484414.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P (Mar 2005). "Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1". Nature. 434 (7029): 113–8. doi:10.1038/nature03354. PMID 15744310.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ ^أ ^ب Nemoto S, Fergusson MM, Finkel T (Apr 2005). "SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1 alpha". J Biol Chem. 280 (16): 16456–60. doi:10.1074/jbc.M501485200. PMID 15716268.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ 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 (Dec 2006). "Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha". Cell. 127 (6): 1109–22. doi:10.1016/j.cell.2006.11.013. PMID 17112576.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Liu Y, Dentin R, Chen D, Hedrick S, Ravnskjaer K, Schenk S, Milne J, Meyers DJ, Cole P, Yates J 3rd, Olefsky J, Guarente L, Montminy M (Nov 2008). "A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange". Nature. 456 (7219): 269–73. doi:10.1038/nature07349. PMC 2597669. PMID 18849969.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
^ Cantó C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, Elliott PJ, Puigserver P, Auwerx J (Apr 2009). "AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity". Nature. 458 (7214): 1056–60. doi:10.1038/nature07813. PMID 19262508.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ ^أ ^ب PMID 23217256 (PubMed)
Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
^ ^أ ^ب Alcaín FJ, Villalba JM (April 2009). "Sirtuin activators". Expert Opin Ther Pat. 19 (4): 403–14. doi:10.1517/13543770902762893. PMID 19441923.
^ Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell SD, Napper A, Curtis R, DiStefano PS, Fields S, Bedalov A, Kennedy BK (April 2005). "Substrate-specific activation of sirtuins by resveratrol". J. Biol. Chem. 280 (17): 17038–45. doi:10.1074/jbc.M500655200. PMID 15684413.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Beher D, Wu J, Cumine S, Kim KW, Lu SC, Atangan L, Wang M (December 2009). "Resveratrol is not a direct activator of SIRT1 enzyme activity". Chem Biol Drug Des. 74 (6): 619–24. doi:10.1111/j.1747-0285.2009.00901.x. PMID 19843076.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Sun C, Zhang F, Ge X, Yan T, Chen X, Shi X, Zhai Q (October 2007). "SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B". Cell Metab. 6 (4): 307–19. doi:10.1016/j.cmet.2007.08.014. PMID 17908559.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Pacholec M, Chrunyk BA, Cunningham D, Flynn D, Griffith DA, Griffor M, Loulakis P, Pabst B, Qiu X, Stockman B, Thanabal V, Varghese A, Ward J, Withka J, Ahn K (January 2010). "SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1". J Biol Chem. 285 (11): 8340–51. doi:10.1074/jbc.M109.088682. PMC 2832984. PMID 20061378.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Takata T, Ishikawa F (January 2003). "Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression". Biochem. Biophys. Res. Commun. 301 (1): 250–7. doi:10.1016/S0006-291X(02)03020-6. PMID 12535671.
^ Strum JC, Johnson JH, Ward J, Xie H, Feild J, Hester A, Alford A, Waters KM (2009). "MicroRNA 132 regulates nutritional stress-induced chemokine production through repression of SirT1". Mol Endocrinol. 23 (11): 1876–84. doi:10.1210/me.2009-0117. PMID 19819989.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Sharma A, Gautam V, Costantini S, Paladino A, Colonna G (2012). "Interactomic and pharmacological insights on human sirt-1". Front Pharmacol. 3: 40. doi:10.3389/fphar.2012.00040. PMC 3311038. PMID 22470339.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)

وصلات خارجية

Corante weblog by Derek Lowe about sir2 and SIRT1 research.
قالب:UCSC genome browser
قالب:UCSC gene details

[pmid10381378-1] 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". Biochem. Biophys. Res. Commun. 260 (1): 273–9. doi:10.1006/bbrc.1999.0897. PMID 10381378.

[entrez-2] أ ^ب "Entrez Gene: SIRT1 sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae)".

[UCSC_SIRT1-3] قالب:UCSC genome browser

[4] Sinclair DA, Guarente L (March 2006). "Unlocking the Secrets of Longevity Genes". Scientific American.

[5] Sun C, Zhang F, Ge X; et al. (October 2007). "SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B". Cell Metab. 6 (4): 307–19. doi:10.1016/j.cmet.2007.08.014. PMID 17908559. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)

[pmid20484414-6] أ ^ب Wilson BJ, Tremblay AM, Deblois G, Sylvain-Drolet G, Giguère V (Jul 2010). "An acetylation switch modulates the transcriptional activity of estrogen-related receptor alpha". Mol. Endocrinol. 24 (7): 1349–58. doi:10.1210/me.2009-0441. PMID 20484414.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[pmid15744310-7] Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P (Mar 2005). "Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1". Nature. 434 (7029): 113–8. doi:10.1038/nature03354. PMID 15744310.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[pmid15716268-8] أ ^ب Nemoto S, Fergusson MM, Finkel T (Apr 2005). "SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1 alpha". J Biol Chem. 280 (16): 16456–60. doi:10.1074/jbc.M501485200. PMID 15716268.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[pmid17112576-9] 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 (Dec 2006). "Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha". Cell. 127 (6): 1109–22. doi:10.1016/j.cell.2006.11.013. PMID 17112576.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[pmid18849969-10] Liu Y, Dentin R, Chen D, Hedrick S, Ravnskjaer K, Schenk S, Milne J, Meyers DJ, Cole P, Yates J 3rd, Olefsky J, Guarente L, Montminy M (Nov 2008). "A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange". Nature. 456 (7219): 269–73. doi:10.1038/nature07349. PMC 2597669. PMID 18849969.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)

[pmid19262508-11] Cantó C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, Elliott PJ, Puigserver P, Auwerx J (Apr 2009). "AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity". Nature. 458 (7214): 1056–60. doi:10.1038/nature07813. PMID 19262508.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[pmid23217256-12] أ ^ب PMID 23217256 (PubMed)
Citation will be completed automatically in a few minutes. Jump the queue or expand by hand

[pmid19441923-13] أ ^ب Alcaín FJ, Villalba JM (April 2009). "Sirtuin activators". Expert Opin Ther Pat. 19 (4): 403–14. doi:10.1517/13543770902762893. PMID 19441923.

[pmid15684413-14] Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell SD, Napper A, Curtis R, DiStefano PS, Fields S, Bedalov A, Kennedy BK (April 2005). "Substrate-specific activation of sirtuins by resveratrol". J. Biol. Chem. 280 (17): 17038–45. doi:10.1074/jbc.M500655200. PMID 15684413.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[pmid19843076-15] Beher D, Wu J, Cumine S, Kim KW, Lu SC, Atangan L, Wang M (December 2009). "Resveratrol is not a direct activator of SIRT1 enzyme activity". Chem Biol Drug Des. 74 (6): 619–24. doi:10.1111/j.1747-0285.2009.00901.x. PMID 19843076.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[pmid17908559-16] Sun C, Zhang F, Ge X, Yan T, Chen X, Shi X, Zhai Q (October 2007). "SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B". Cell Metab. 6 (4): 307–19. doi:10.1016/j.cmet.2007.08.014. PMID 17908559.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[pmid20061378-17] Pacholec M, Chrunyk BA, Cunningham D, Flynn D, Griffith DA, Griffor M, Loulakis P, Pabst B, Qiu X, Stockman B, Thanabal V, Varghese A, Ward J, Withka J, Ahn K (January 2010). "SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1". J Biol Chem. 285 (11): 8340–51. doi:10.1074/jbc.M109.088682. PMC 2832984. PMID 20061378.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[pmid12535671-18] Takata T, Ishikawa F (January 2003). "Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression". Biochem. Biophys. Res. Commun. 301 (1): 250–7. doi:10.1016/S0006-291X(02)03020-6. PMID 12535671.

[pmid19819989-19] Strum JC, Johnson JH, Ward J, Xie H, Feild J, Hester A, Alford A, Waters KM (2009). "MicroRNA 132 regulates nutritional stress-induced chemokine production through repression of SirT1". Mol Endocrinol. 23 (11): 1876–84. doi:10.1210/me.2009-0117. PMID 19819989.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[pmid22470339-20] Sharma A, Gautam V, Costantini S, Paladino A, Colonna G (2012). "Interactomic and pharmacological insights on human sirt-1". Front Pharmacol. 3: 40. doi:10.3389/fphar.2012.00040. PMC 3311038. PMID 22470339.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)

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