[{"@context":"http:\/\/schema.org\/","@type":"BlogPosting","@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/tsc2-wikipedia\/#BlogPosting","mainEntityOfPage":"https:\/\/wiki.edu.vn\/en\/wiki24\/tsc2-wikipedia\/","headline":"TSC2 &#8211; Wikipedia","name":"TSC2 &#8211; Wikipedia","description":"before-content-x4 From Wikipedia, the free encyclopedia after-content-x4 Mammalian protein found in Homo sapiens Tuberous Sclerosis Complex 2 (TSC2), also known","datePublished":"2022-12-05","dateModified":"2022-12-05","author":{"@type":"Person","@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/author\/lordneo\/#Person","name":"lordneo","url":"https:\/\/wiki.edu.vn\/en\/wiki24\/author\/lordneo\/","image":{"@type":"ImageObject","@id":"https:\/\/secure.gravatar.com\/avatar\/c9645c498c9701c88b89b8537773dd7c?s=96&d=mm&r=g","url":"https:\/\/secure.gravatar.com\/avatar\/c9645c498c9701c88b89b8537773dd7c?s=96&d=mm&r=g","height":96,"width":96}},"publisher":{"@type":"Organization","name":"Enzyklop\u00e4die","logo":{"@type":"ImageObject","@id":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","url":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","width":600,"height":60}},"image":{"@type":"ImageObject","@id":"https:\/\/en.wikipedia.org\/wiki\/Special:CentralAutoLogin\/start?type=1x1","url":"https:\/\/en.wikipedia.org\/wiki\/Special:CentralAutoLogin\/start?type=1x1","height":"1","width":"1"},"url":"https:\/\/wiki.edu.vn\/en\/wiki24\/tsc2-wikipedia\/","about":["Wiki"],"wordCount":9726,"articleBody":"     (adsbygoogle = window.adsbygoogle || []).push({});before-content-x4From Wikipedia, the free encyclopedia       (adsbygoogle = window.adsbygoogle || []).push({});after-content-x4Mammalian protein found in Homo sapiensTuberous Sclerosis Complex 2 (TSC2), also known as Tuberin, is a protein that in humans is encoded by the TSC2 gene.       (adsbygoogle = window.adsbygoogle || []).push({});after-content-x4Table of ContentsFunction[edit]Cell Pathology[edit]Signaling Pathways[edit]Interactions[edit]See also[edit]References[edit]Further reading[edit]External links[edit]Function[edit]Mutations in this gene lead to tuberous sclerosis. Its gene product is believed to be a tumor suppressor and is able to stimulate specific GTPases. Hamartin coded by the gene TSC1 functions as a facilitator of Hsp90 in chaperoning of Tuberin, therefore preventing its ubiquitination and degradation in the proteasome.[5]Alternative splicing results in multiple transcript variants encoding different isoforms of the protein.[6]  Mutations in TSC2 can cause Lymphangioleiomyomatosis, a disease caused by the enlargement of tissue in the lungs, creating cysts and tumours and causing difficulty breathing.  Because Tuberin regulates cell size, along with the protein Hamartin, mutations to TSC1 and TSC2 genes may prevent the control of cell growth in the lungs of individuals.[5]Cell Pathology[edit]Cells from individuals with pathogenic mutations in the TSC2 gene display depletion of lysosomes, impairment of autophagy, and abnormal accumulation of glycogen. Defects in the autophagy-lysosome pathway are associated with excessive ubiquitination and degradation of LC3 and LAMP1\/2 proteins.[7]       (adsbygoogle = window.adsbygoogle || []).push({});after-content-x4Signaling Pathways[edit]Pharmacological inhibition of ERK1\/2 restores GSK3\u03b2 activity and protein synthesis levels in a model of tuberous sclerosis.[8]The defective degradation of glycogen by the autophagy-lysosome pathway is, at least in part, independent of impaired regulation of mTORC1 and is restored by the combined use of PKB\/Akt and mTORC1 pharmacological inhibitors.[7]Interactions[edit]TSC2 functions within a multi-protein complex knowns as the TSC complex which consists of the core proteins TSC2, TSC1,[9][10] and TBC1D7.TSC2 has been reported to interact with several other proteins that are not a part of the TSC complex including:AKT1,[11][12]AXIN1,[13]FOXO1,[14]GSK3B,[13][15]Hsp70[5]Hsp90[5]MAPK1,[16]PTK2,[17]PAM,[18]PRKAA1,[19][20]RAP1A,[21][22]RHEB,[14][21][23][24][25][26]RPS6KA1,[12][27]UBE3A[28][29]  andYWHAZ.[30]See also[edit]References[edit]^ a b c GRCh38: Ensembl release 89: ENSG00000103197 &#8211; Ensembl, May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000002496 &#8211; Ensembl, May 2017^ &#8220;Human PubMed Reference:&#8221;. National Center for Biotechnology Information, U.S. National Library of Medicine.^ &#8220;Mouse PubMed Reference:&#8221;. National Center for Biotechnology Information, U.S. National Library of Medicine.^ a b c d Woodford MR, Sager RA, Marris E, Dunn DM, Blanden AR, Murphy RL, Rensing N, Shapiro O, Panaretou B, Prodromou C, Loh SN, Gutmann DH, Bourboulia D, Bratslavsky G, Wong M, Mollapour M (December 2017). &#8220;Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding of kinase and non-kinase clients&#8221;. The EMBO Journal. 36 (24): 3650\u20133665. doi:10.15252\/embj.201796700. PMC\u00a05730846. PMID\u00a029127155.^ &#8220;Entrez Gene: TSC2 tuberous sclerosis 2&#8221;.^ a b Pal R, Xiong Y, Sardiello M (February 2019). &#8220;Abnormal glycogen storage in tuberous sclerosis complex caused by impairment of mTORC1-dependent and -independent signaling pathways&#8221;. Proc Natl Acad Sci U S A. 116 (8): 2977\u20132986. doi:10.1073\/pnas.1812943116. PMC\u00a06386676. PMID\u00a030728291.^ Pal R, Bondar VV, Adamski CJ, Rodney GG, Sardiello M (June 2017). &#8220;Inhibition of ERK1\/2 Restores GSK3\u03b2 Activity and Protein Synthesis Levels in a Model of Tuberous Sclerosis&#8221;. Scientific Reports. 7 (1): 4174. doi:10.1038\/s41598-017-04528-5. PMC\u00a05482840. PMID\u00a028646232.^ Orlova KA, Crino PB (January 2010). &#8220;The tuberous sclerosis complex&#8221;. Annals of the New York Academy of Sciences. 1184: 87\u2013105. doi:10.1111\/j.1749-6632.2009.05117.x. PMC\u00a02892799. PMID\u00a020146692.^ Li Y, Inoki K, Guan KL (September 2004). &#8220;Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity&#8221;. Molecular and Cellular Biology. 24 (18): 7965\u201375. doi:10.1128\/MCB.24.18.7965-7975.2004. PMC\u00a0515062. PMID\u00a015340059.^ Dan HC, Sun M, Yang L, Feldman RI, Sui XM, Ou CC, Nellist M, Yeung RS, Halley DJ, Nicosia SV, Pledger WJ, Cheng JQ (September 2002). &#8220;Phosphatidylinositol 3-kinase\/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin&#8221;. The Journal of Biological Chemistry. 277 (38): 35364\u201370. doi:10.1074\/jbc.M205838200. PMID\u00a012167664.^ a b Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J (September 2004). &#8220;Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase&#8221;. Proceedings of the National Academy of Sciences of the United States of America. 101 (37): 13489\u201394. doi:10.1073\/pnas.0405659101. PMC\u00a0518784. PMID\u00a015342917.^ a b Mak BC, Takemaru K, Kenerson HL, Moon RT, Yeung RS (February 2003). &#8220;The tuberin-hamartin complex negatively regulates beta-catenin signaling activity&#8221;. The Journal of Biological Chemistry. 278 (8): 5947\u201351. doi:10.1074\/jbc.C200473200. PMID\u00a012511557.^ a b Cao Y, Kamioka Y, Yokoi N, Kobayashi T, Hino O, Onodera M, Mochizuki N, Nakae J (December 2006). &#8220;Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin\/p70 S6K pathway&#8221;. The Journal of Biological Chemistry. 281 (52): 40242\u201351. doi:10.1074\/jbc.M608116200. PMID\u00a017077083.^ Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, Yang Q, Bennett C, Harada Y, Stankunas K, Wang CY, He X, MacDougald OA, You M, Williams BO, Guan KL (September 2006). &#8220;TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth&#8221;. Cell. 126 (5): 955\u201368. doi:10.1016\/j.cell.2006.06.055. PMID\u00a016959574. S2CID\u00a016047397.^ Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP (April 2005). &#8220;Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis&#8221;. Cell. 121 (2): 179\u201393. doi:10.1016\/j.cell.2005.02.031. PMID\u00a015851026. S2CID\u00a018663447.^ Gan B, Yoo Y, Guan JL (December 2006). &#8220;Association of focal adhesion kinase with tuberous sclerosis complex 2 in the regulation of s6 kinase activation and cell growth&#8221;. The Journal of Biological Chemistry. 281 (49): 37321\u20139. doi:10.1074\/jbc.M605241200. PMID\u00a017043358.^ Murthy V, Han S, Beauchamp RL, Smith N, Haddad LA, Ito N, Ramesh V (January 2004). &#8220;Pam and its ortholog highwire interact with and may negatively regulate the TSC1.TSC2 complex&#8221;. The Journal of Biological Chemistry. 279 (2): 1351\u20138. doi:10.1074\/jbc.M310208200. PMID\u00a014559897.^ Inoki K, Zhu T, Guan KL (November 2003). &#8220;TSC2 mediates cellular energy response to control cell growth and survival&#8221;. Cell. 115 (5): 577\u201390. doi:10.1016\/S0092-8674(03)00929-2. PMID\u00a014651849. S2CID\u00a018173817.^ Shaw RJ, Bardeesy N, Manning BD, Lopez L, Kosmatka M, DePinho RA, Cantley LC (July 2004). &#8220;The LKB1 tumor suppressor negatively regulates mTOR signaling&#8221;. Cancer Cell. 6 (1): 91\u20139. doi:10.1016\/j.ccr.2004.06.007. PMID\u00a015261145.^ a b Castro AF, Rebhun JF, Clark GJ, Quilliam LA (August 2003). &#8220;Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner&#8221;. The Journal of Biological Chemistry. 278 (35): 32493\u20136. doi:10.1074\/jbc.C300226200. PMID\u00a012842888.^ Yamamoto Y, Jones KA, Mak BC, Muehlenbachs A, Yeung RS (August 2002). &#8220;Multicompartmental distribution of the tuberous sclerosis gene products, hamartin and tuberin&#8221;. Archives of Biochemistry and Biophysics. 404 (2): 210\u20137. doi:10.1016\/S0003-9861(02)00300-4. PMID\u00a012147258.^ Inoki K, Li Y, Xu T, Guan KL (August 2003). &#8220;Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling&#8221;. Genes &#038; Development. 17 (15): 1829\u201334. doi:10.1101\/gad.1110003. PMC\u00a0196227. PMID\u00a012869586.^ Garami A, Zwartkruis FJ, Nobukuni T, Joaquin M, Roccio M, Stocker H, Kozma SC, Hafen E, Bos JL, Thomas G (June 2003). &#8220;Insulin activation of Rheb, a mediator of mTOR\/S6K\/4E-BP signaling, is inhibited by TSC1 and 2&#8221; (PDF). Molecular Cell. 11 (6): 1457\u201366. doi:10.1016\/S1097-2765(03)00220-X. PMID\u00a012820960.^ Zhang Y, Gao X, Saucedo LJ, Ru B, Edgar BA, Pan D (June 2003). &#8220;Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins&#8221;. Nature Cell Biology. 5 (6): 578\u201381. doi:10.1038\/ncb999. PMID\u00a012771962. S2CID\u00a013451385.^ Long X, Lin Y, Ortiz-Vega S, Yonezawa K, Avruch J (April 2005). &#8220;Rheb binds and regulates the mTOR kinase&#8221;. Current Biology. 15 (8): 702\u201313. doi:10.1016\/j.cub.2005.02.053. PMID\u00a015854902. S2CID\u00a03078706.^ Rolfe M, McLeod LE, Pratt PF, Proud CG (June 2005). &#8220;Activation of protein synthesis in cardiomyocytes by the hypertrophic agent phenylephrine requires the activation of ERK and involves phosphorylation of tuberous sclerosis complex 2 (TSC2)&#8221;. The Biochemical Journal. 388 (Pt 3): 973\u201384. doi:10.1042\/BJ20041888. PMC\u00a01183479. PMID\u00a015757502.^ Lu Z, Hu X, Li Y, Zheng L, Zhou Y, Jiang H, Ning T, Basang Z, Zhang C, Ke Y (August 2004). &#8220;Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin&#8221;. The Journal of Biological Chemistry. 279 (34): 35664\u201370. doi:10.1074\/jbc.M403385200. PMID\u00a015175323.^ Zheng L, Ding H, Lu Z, Li Y, Pan Y, Ning T, Ke Y (March 2008). &#8220;E3 ubiquitin ligase E6AP-mediated TSC2 turnover in the presence and absence of HPV16 E6&#8221;. Genes to Cells. 13 (3): 285\u201394. doi:10.1111\/j.1365-2443.2008.01162.x. PMID\u00a018298802. S2CID\u00a025851829.^ Nellist M, Goedbloed MA, de Winter C, Verhaaf B, Jankie A, Reuser AJ, van den Ouweland AM, van der Sluijs P, Halley DJ (October 2002). &#8220;Identification and characterization of the interaction between tuberin and 14-3-3zeta&#8221;. The Journal of Biological Chemistry. 277 (42): 39417\u201324. doi:10.1074\/jbc.M204802200. PMID\u00a012176984.Further reading[edit]Jones AC, Shyamsundar MM, Thomas MW, Maynard J, Idziaszczyk S, Tomkins S, Sampson JR, Cheadle JP (May 1999). &#8220;Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis&#8221;. American Journal of Human Genetics. 64 (5): 1305\u201315. doi:10.1086\/302381. PMC\u00a01377866. PMID\u00a010205261.Hengstschl\u00e4ger M (August 2001). &#8220;Tuberous sclerosis complex genes: from flies to human genetics&#8221;. Archives of Dermatological Research. 293 (8): 383\u20136. doi:10.1007\/s004030100250. PMID\u00a011686512. S2CID\u00a035702323.Hockenbery DM (February 2003). &#8220;Nailing down a link between tuberin and renal cysts&#8221;. The American Journal of Pathology. 162 (2): 369\u201371. doi:10.1016\/S0002-9440(10)63831-X. PMC\u00a01851147. PMID\u00a012547695.Ramesh V (June 2003). &#8220;Aspects of tuberous sclerosis complex (TSC) protein function in the brain&#8221;. Biochemical Society Transactions. 31 (Pt 3): 579\u201383. doi:10.1042\/BST0310579. PMID\u00a012773159.Knowles MA, Hornigold N, Pitt E (June 2003). &#8220;Tuberous sclerosis complex (TSC) gene involvement in sporadic tumours&#8221;. Biochemical Society Transactions. 31 (Pt 3): 597\u2013602. doi:10.1042\/BST0310597. PMID\u00a012773163.Ellisen LW (November 2005). &#8220;Growth control under stress: mTOR regulation through the REDD1-TSC pathway&#8221;. Cell Cycle. 4 (11): 1500\u201302. doi:10.4161\/cc.4.11.2139. PMID\u00a016258273.Jozwiak J, Jozwiak S (March 2007). &#8220;Giant cells: contradiction to two-hit model of tuber formation?&#8221;. Cellular and Molecular Neurobiology. 27 (2): 251\u201361. doi:10.1007\/s10571-006-9106-0. PMID\u00a016897363. S2CID\u00a031624726.Cai SL, Walker CL (January 2006). &#8220;TSC2, a key player in tumor suppression and cystic kidney disease&#8221;. Nephrologie &#038; Therapeutique. 2 Suppl 2: S119-22. PMID\u00a017373211.Urban T (June 2007). &#8220;[Pulmonary lymphangioleiomyomatosis with or without tuberous sclerosis]&#8221;. Revue des Maladies Respiratoires. 24 (6): 725\u201340. doi:10.1016\/S0761-8425(07)91147-X. PMID\u00a017632432.External links[edit]       (adsbygoogle = window.adsbygoogle || []).push({});after-content-x4"},{"@context":"http:\/\/schema.org\/","@type":"BreadcrumbList","itemListElement":[{"@type":"ListItem","position":1,"item":{"@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/#breadcrumbitem","name":"Enzyklop\u00e4die"}},{"@type":"ListItem","position":2,"item":{"@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/tsc2-wikipedia\/#breadcrumbitem","name":"TSC2 &#8211; Wikipedia"}}]}]