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a fleshy underground stem or root serving for reproductive and food storage

PrepTutorEJDIC

塊茎(ジャガイモのような塊状の地下室茎)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/10/03 19:18:50」(JST)

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Tuberous Sclerosis Complex 2 (TSC2), also known as Tuberin, is a protein that in humans is encoded by the TSC2 gene.

Function

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. The protein associates with hamartin in a cytosolic complex, possibly acting as a chaperone for hamartin. Alternative splicing results in multiple transcript variants encoding different isoforms of the protein.^[1] Together with tuberous sclerosis, 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 coded by the gene TSC1, mutations to these genes may prevent the control of cell growth in the lungs of individuals.^[2]

Interactions

TSC2 functions within a multi-protein complex knowns as the TSC complex which consists of the core proteins TSC2, TSC1,^[3]^[4] and TBC1D7.

TSC2 has been reported to interact with several other proteins that are not a part of the TSC complex including:

AKT1,^[5]^[6]
AXIN1,^[7]
FOXO1,^[8]
GSK3B,^[7]^[9]
MAPK1,^[10]
PTK2,^[11]
PAM,^[12]
PRKAA1,^[13]^[14]
RAP1A,^[15]^[16]
RHEB,^[8]^[15]^[17]^[18]^[19]^[20]
RPS6KA1,^[6]^[21]
UBE3A^[22]^[23] and
YWHAZ.^[24]

References

^ "Entrez Gene: TSC2 tuberous sclerosis 2".
^ "Lymphangioleiomyomatosis". Genetics Home Reference. Retrieved 28 September 2015.
^ Orlova KA, Crino PB (2010). "The tuberous sclerosis complex". Ann. N. Y. Acad. Sci. 1184: 87–105. doi:10.1111/j.1749-6632.2009.05117.x. PMC 2892799. PMID 20146692.
^ Li Y, Inoki K, Guan KL (2004). "Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity". Mol. Cell. Biol. 24 (18): 7965–75. doi:10.1128/MCB.24.18.7965-7975.2004. PMC 515062. PMID 15340059.
^ Dan HC, Sun M, Yang L, Feldman RI, Sui XM, Ou CC, Nellist M, Yeung RS, Halley DJ, Nicosia SV, Pledger WJ, Cheng JQ (2002). "Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin". J. Biol. Chem. 277 (38): 35364–70. doi:10.1074/jbc.M205838200. PMID 12167664.
^ ^a ^b Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J (2004). "Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase". Proc. Natl. Acad. Sci. U.S.A. 101 (37): 13489–94. doi:10.1073/pnas.0405659101. PMC 518784. PMID 15342917.
^ ^a ^b Mak BC, Takemaru K, Kenerson HL, Moon RT, Yeung RS (2003). "The tuberin-hamartin complex negatively regulates beta-catenin signaling activity". J. Biol. Chem. 278 (8): 5947–51. doi:10.1074/jbc.C200473200. PMID 12511557.
^ ^a ^b Cao Y, Kamioka Y, Yokoi N, Kobayashi T, Hino O, Onodera M, Mochizuki N, Nakae J (2006). "Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway". J. Biol. Chem. 281 (52): 40242–51. doi:10.1074/jbc.M608116200. PMID 17077083.
^ 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 (2006). "TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth". Cell 126 (5): 955–68. doi:10.1016/j.cell.2006.06.055. PMID 16959574.
^ Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP (2005). "Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis". Cell 121 (2): 179–93. doi:10.1016/j.cell.2005.02.031. PMID 15851026.
^ Gan B, Yoo Y, Guan JL (2006). "Association of focal adhesion kinase with tuberous sclerosis complex 2 in the regulation of s6 kinase activation and cell growth". J. Biol. Chem. 281 (49): 37321–9. doi:10.1074/jbc.M605241200. PMID 17043358.
^ Murthy V, Han S, Beauchamp RL, Smith N, Haddad LA, Ito N, Ramesh V (2004). "Pam and its ortholog highwire interact with and may negatively regulate the TSC1.TSC2 complex". J. Biol. Chem. 279 (2): 1351–8. doi:10.1074/jbc.M310208200. PMID 14559897.
^ Inoki K, Zhu T, Guan KL (2003). "TSC2 mediates cellular energy response to control cell growth and survival". Cell 115 (5): 577–90. doi:10.1016/S0092-8674(03)00929-2. PMID 14651849.
^ Shaw RJ, Bardeesy N, Manning BD, Lopez L, Kosmatka M, DePinho RA, Cantley LC (2004). "The LKB1 tumor suppressor negatively regulates mTOR signaling". Cancer Cell 6 (1): 91–9. doi:10.1016/j.ccr.2004.06.007. PMID 15261145.
^ ^a ^b Castro AF, Rebhun JF, Clark GJ, Quilliam LA (2003). "Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner". J. Biol. Chem. 278 (35): 32493–6. doi:10.1074/jbc.C300226200. PMID 12842888.
^ Yamamoto Y, Jones KA, Mak BC, Muehlenbachs A, Yeung RS (2002). "Multicompartmental distribution of the tuberous sclerosis gene products, hamartin and tuberin". Arch. Biochem. Biophys. 404 (2): 210–7. doi:10.1016/S0003-9861(02)00300-4. PMID 12147258.
^ Inoki K, Li Y, Xu T, Guan KL (2003). "Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling". Genes Dev. 17 (15): 1829–34. doi:10.1101/gad.1110003. PMC 196227. PMID 12869586.
^ Garami A, Zwartkruis FJ, Nobukuni T, Joaquin M, Roccio M, Stocker H, Kozma SC, Hafen E, Bos JL, Thomas G (2003). "Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2". Mol. Cell 11 (6): 1457–66. doi:10.1016/S1097-2765(03)00220-X. PMID 12820960.
^ Zhang Y, Gao X, Saucedo LJ, Ru B, Edgar BA, Pan D (2003). "Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins". Nat. Cell Biol. 5 (6): 578–81. doi:10.1038/ncb999. PMID 12771962.
^ Long X, Lin Y, Ortiz-Vega S, Yonezawa K, Avruch J (2005). "Rheb binds and regulates the mTOR kinase". Curr. Biol. 15 (8): 702–13. doi:10.1016/j.cub.2005.02.053. PMID 15854902.
^ Rolfe M, McLeod LE, Pratt PF, Proud CG (2005). "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)". Biochem. J. 388 (Pt 3): 973–84. doi:10.1042/BJ20041888. PMC 1183479. PMID 15757502.
^ Lu Z, Hu X, Li Y, Zheng L, Zhou Y, Jiang H, Ning T, Basang Z, Zhang C, Ke Y (2004). "Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin". J. Biol. Chem. 279 (34): 35664–70. doi:10.1074/jbc.M403385200. PMID 15175323.
^ Zheng L, Ding H, Lu Z, Li Y, Pan Y, Ning T, Ke Y (2008). "E3 ubiquitin ligase E6AP-mediated TSC2 turnover in the presence and absence of HPV16 E6". Genes Cells 13 (3): 285–94. doi:10.1111/j.1365-2443.2008.01162.x. PMID 18298802.
^ Nellist M, Goedbloed MA, de Winter C, Verhaaf B, Jankie A, Reuser AJ, van den Ouweland AM, van der Sluijs P, Halley DJ (2002). "Identification and characterization of the interaction between tuberin and 14-3-3zeta". J. Biol. Chem. 277 (42): 39417–24. doi:10.1074/jbc.M204802200. PMID 12176984.

External links

GeneReviews/NIH/NCBI/UW entry on Tuberous Sclerosis Complex or Bourneville Disease

This article on a gene on human chromosome 16 is a stub. You can help Wikipedia by expanding it.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 結節性硬化症 tuberous sclerosis complex
2. 結節性硬化症における肺病変 pulmonary involvement in tuberous sclerosis
3. 肺リンパ脈管筋腫症 pulmonary lymphangioleiomyomatosis
4. 遺伝性腎癌症候群 hereditary kidney cancer syndromes
5. 結節性硬化症および腎血管筋脂肪腫の腎症状 renal manifestations of tuberous sclerosis and renal angiomyolipoma

English Journal

Tuberous sclerosis complex: Recent advances in manifestations and therapy.

Wataya-Kaneda M1, Uemura M2, Fujita K2, Hirata H3, Osuga K4, Kagitani-Shimono K5, Nonomura N2; Tuberous Sclerosis Complex Board of Osaka University Hospital.
International journal of urology : official journal of the Japanese Urological Association.Int J Urol.2017 Jul 1. doi: 10.1111/iju.13390. [Epub ahead of print]
PMID 28667702

Responses of skeletal muscle hypertrophy in Wistar rats to different resistance exercise models.

Luciano TF1, Marques SO, Pieri BL, de Souza DR, Araújo LV, Nesi RT, Scheffer DL, Comin VH, Pinho RA, Muller AP, de Souza CT.
Physiological research.Physiol Res.2017 May 4;66(2):317-323. Epub 2016 Dec 16.
PMID 27982685

Phenotypic and genotypic characterization of Chinese children diagnosed with tuberous sclerosis complex.

Yang G1, Shi ZN2, Meng Y1, Shi XY1, Pang LY1, Ma SF1, Zhang MN1, Wang YY1, Zou LP1,3.
Clinical genetics.Clin Genet.2017 May;91(5):764-768. doi: 10.1111/cge.12920. Epub 2017 Feb 22.
PMID 27859028

Japanese Journal

神経皮膚症候群研究の進歩 : NF1(神経線維腫症1型)とTSC(結節性硬化症)

脳と発達 42(2), 150-152, 2010-03-01
NAID 10026528298

Hamartin-Hsp70 Interaction Is Necessary for Akt-Dependent Tuberin Phosphorylation during Heat Shock

Bioscience, biotechnology, and biochemistry 73(11), 2488-2493, 2009-11-23
NAID 10027548025

結節性硬化症の分子病態と新しい治療法 (皮膚科領域の特定疾患)

医学のあゆみ 230(11), 981-986, 2009-09-12
NAID 40016716198

Related Pictures

★リンクテーブル★

リンク元	「ツベリン」
関連記事	「tuber」

「ツベリン」

Tuberous sclerosis 2
Identifiers
Symbols	TSC2 ; LAM; PPP1R160; TSC4
External IDs	OMIM: 191092 MGI: 102548 HomoloGene: 462 GeneCards: TSC2 Gene
Gene ontology
Molecular function	• GTPase activator activity; • protein binding; • phosphatase binding; • small GTPase binding; • protein homodimerization activity; • 14-3-3 protein binding;
Cellular component	• nucleus; • cytoplasm; • lysosome; • Golgi apparatus; • cytosol; • membrane; • TSC1-TSC2 complex; • perinuclear region of cytoplasm;
Biological process	• response to hypoxia; • neural tube closure; • transcription initiation from RNA polymerase II promoter; • negative regulation of protein kinase activity; • protein import into nucleus; • endocytosis; • cell cycle arrest; • epidermal growth factor receptor signaling pathway; • heart development; • protein localization; • negative regulation of cell proliferation; • insulin receptor signaling pathway; • fibroblast growth factor receptor signaling pathway; • gene expression; • phosphatidylinositol 3-kinase signaling; • negative regulation of phosphatidylinositol 3-kinase signaling; • viral process; • vesicle-mediated transport; • regulation of endocytosis; • negative regulation of Wnt signaling pathway; • negative regulation of TOR signaling; • Fc-epsilon receptor signaling pathway; • protein kinase B signaling; • positive regulation of GTPase activity; • protein transport into plasma membrane raft; • innate immune response; • positive regulation of transcription from RNA polymerase II promoter; • glucose import; • regulation of insulin receptor signaling pathway; • negative regulation of insulin receptor signaling pathway; • insulin-like growth factor receptor signaling pathway; • neurotrophin TRK receptor signaling pathway; • phosphatidylinositol-mediated signaling; • positive chemotaxis; • regulation of small GTPase mediated signal transduction; • regulation of cell cycle; • negative regulation of protein kinase B signaling;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;

　　[★]

英: tuberin

結節性硬化症原因遺伝子TSC2産物

「tuber」

　　[★]

n.

隆起、(植物;ジャガイモなどの)塊茎

同: 虫部隆起
関: bulge、eminence、plant tuber、protrude、protrusion、protuberance、swelling、tuberosity

[1] "Entrez Gene: TSC2 tuberous sclerosis 2".

[2] "Lymphangioleiomyomatosis". Genetics Home Reference. Retrieved 28 September 2015.

[pmid20146692-3] Orlova KA, Crino PB (2010). "The tuberous sclerosis complex". Ann. N. Y. Acad. Sci. 1184: 87–105. doi:10.1111/j.1749-6632.2009.05117.x. PMC 2892799. PMID 20146692.

[pmid15340059-4] Li Y, Inoki K, Guan KL (2004). "Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity". Mol. Cell. Biol. 24 (18): 7965–75. doi:10.1128/MCB.24.18.7965-7975.2004. PMC 515062. PMID 15340059.

[pmid12167664-5] Dan HC, Sun M, Yang L, Feldman RI, Sui XM, Ou CC, Nellist M, Yeung RS, Halley DJ, Nicosia SV, Pledger WJ, Cheng JQ (2002). "Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin". J. Biol. Chem. 277 (38): 35364–70. doi:10.1074/jbc.M205838200. PMID 12167664.

[pmid15342917-6] Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J (2004). "Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase". Proc. Natl. Acad. Sci. U.S.A. 101 (37): 13489–94. doi:10.1073/pnas.0405659101. PMC 518784. PMID 15342917.

[pmid12511557-7] Mak BC, Takemaru K, Kenerson HL, Moon RT, Yeung RS (2003). "The tuberin-hamartin complex negatively regulates beta-catenin signaling activity". J. Biol. Chem. 278 (8): 5947–51. doi:10.1074/jbc.C200473200. PMID 12511557.

[pmid17077083-8] Cao Y, Kamioka Y, Yokoi N, Kobayashi T, Hino O, Onodera M, Mochizuki N, Nakae J (2006). "Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway". J. Biol. Chem. 281 (52): 40242–51. doi:10.1074/jbc.M608116200. PMID 17077083.

[pmid16959574-9] 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 (2006). "TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth". Cell 126 (5): 955–68. doi:10.1016/j.cell.2006.06.055. PMID 16959574.

[pmid15851026-10] Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP (2005). "Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis". Cell 121 (2): 179–93. doi:10.1016/j.cell.2005.02.031. PMID 15851026.

[pmid17043358-11] Gan B, Yoo Y, Guan JL (2006). "Association of focal adhesion kinase with tuberous sclerosis complex 2 in the regulation of s6 kinase activation and cell growth". J. Biol. Chem. 281 (49): 37321–9. doi:10.1074/jbc.M605241200. PMID 17043358.

[pmid14559897-12] Murthy V, Han S, Beauchamp RL, Smith N, Haddad LA, Ito N, Ramesh V (2004). "Pam and its ortholog highwire interact with and may negatively regulate the TSC1.TSC2 complex". J. Biol. Chem. 279 (2): 1351–8. doi:10.1074/jbc.M310208200. PMID 14559897.

[pmid14651849-13] Inoki K, Zhu T, Guan KL (2003). "TSC2 mediates cellular energy response to control cell growth and survival". Cell 115 (5): 577–90. doi:10.1016/S0092-8674(03)00929-2. PMID 14651849.

[pmid15261145-14] Shaw RJ, Bardeesy N, Manning BD, Lopez L, Kosmatka M, DePinho RA, Cantley LC (2004). "The LKB1 tumor suppressor negatively regulates mTOR signaling". Cancer Cell 6 (1): 91–9. doi:10.1016/j.ccr.2004.06.007. PMID 15261145.

[pmid12842888-15] Castro AF, Rebhun JF, Clark GJ, Quilliam LA (2003). "Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner". J. Biol. Chem. 278 (35): 32493–6. doi:10.1074/jbc.C300226200. PMID 12842888.

[pmid12147258-16] Yamamoto Y, Jones KA, Mak BC, Muehlenbachs A, Yeung RS (2002). "Multicompartmental distribution of the tuberous sclerosis gene products, hamartin and tuberin". Arch. Biochem. Biophys. 404 (2): 210–7. doi:10.1016/S0003-9861(02)00300-4. PMID 12147258.

[pmid12869586-17] Inoki K, Li Y, Xu T, Guan KL (2003). "Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling". Genes Dev. 17 (15): 1829–34. doi:10.1101/gad.1110003. PMC 196227. PMID 12869586.

[pmid12820960-18] Garami A, Zwartkruis FJ, Nobukuni T, Joaquin M, Roccio M, Stocker H, Kozma SC, Hafen E, Bos JL, Thomas G (2003). "Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2". Mol. Cell 11 (6): 1457–66. doi:10.1016/S1097-2765(03)00220-X. PMID 12820960.

[pmid12771962-19] Zhang Y, Gao X, Saucedo LJ, Ru B, Edgar BA, Pan D (2003). "Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins". Nat. Cell Biol. 5 (6): 578–81. doi:10.1038/ncb999. PMID 12771962.

[pmid15854902-20] Long X, Lin Y, Ortiz-Vega S, Yonezawa K, Avruch J (2005). "Rheb binds and regulates the mTOR kinase". Curr. Biol. 15 (8): 702–13. doi:10.1016/j.cub.2005.02.053. PMID 15854902.

[pmid15757502-21] Rolfe M, McLeod LE, Pratt PF, Proud CG (2005). "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)". Biochem. J. 388 (Pt 3): 973–84. doi:10.1042/BJ20041888. PMC 1183479. PMID 15757502.

[pmid15175323-22] Lu Z, Hu X, Li Y, Zheng L, Zhou Y, Jiang H, Ning T, Basang Z, Zhang C, Ke Y (2004). "Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin". J. Biol. Chem. 279 (34): 35664–70. doi:10.1074/jbc.M403385200. PMID 15175323.

[pmid18298802-23] Zheng L, Ding H, Lu Z, Li Y, Pan Y, Ning T, Ke Y (2008). "E3 ubiquitin ligase E6AP-mediated TSC2 turnover in the presence and absence of HPV16 E6". Genes Cells 13 (3): 285–94. doi:10.1111/j.1365-2443.2008.01162.x. PMID 18298802.

[pmid12176984-24] Nellist M, Goedbloed MA, de Winter C, Verhaaf B, Jankie A, Reuser AJ, van den Ouweland AM, van der Sluijs P, Halley DJ (2002). "Identification and characterization of the interaction between tuberin and 14-3-3zeta". J. Biol. Chem. 277 (42): 39417–24. doi:10.1074/jbc.M204802200. PMID 12176984.

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案内

案内

tuberin