TSC1
Tuberous sclerosis protein 1, also known as TSC1 or hamartin, is a human protein and gene.[1]
Function
This peripheral membrane protein was implicated as a tumor suppressor. It may be also involved in vesicular transport and docking, in complex with TSC2.
Clinical significance
Defects in this gene may cause tuberous sclerosis, due to a functional impairment of the hamartin-tuberin complex. Defects in TSC1 may also be a cause of focal cortical dysplasia.
Interactions
TSC1 has been shown to interact with PLK1,[2] TSC2,[3][4][5][2][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] AKT1[3][21] and NEFL.[22]
See also
References
- ^ "Entrez Gene: TSC1 tuberous sclerosis 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7248.
- ^ a b Astrinidis, Aristotelis; Senapedis William, Henske Elizabeth P (Jan. 2006). "Hamartin, the tuberous sclerosis complex 1 gene product, interacts with polo-like kinase 1 in a phosphorylation-dependent manner". Hum. Mol. Genet. (England) 15 (2): 287–97. doi:10.1093/hmg/ddi444. ISSN 0964-6906. PMID 16339216.
- ^ a b Dan, Han C; Sun Mei, Yang Lin, Feldman Richard I, Sui Xue-Mei, Ou Chien Chen, Nellist Mark, Yeung Raymond S, Halley Dicky J J, Nicosia Santo V, Pledger Warren J, Cheng Jin Q (Sep. 2002). "Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin". J. Biol. Chem. (United States) 277 (38): 35364–70. doi:10.1074/jbc.M205838200. ISSN 0021-9258. PMID 12167664.
- ^ Hodges, A K; Li S, Maynard J, Parry L, Braverman R, Cheadle J P, DeClue J E, Sampson J R (Dec. 2001). "Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin". Hum. Mol. Genet. (England) 10 (25): 2899–905. doi:10.1093/hmg/10.25.2899. ISSN 0964-6906. PMID 11741833.
- ^ Aicher, L D; Campbell J S, Yeung R S (Jun. 2001). "Tuberin phosphorylation regulates its interaction with hamartin. Two proteins involved in tuberous sclerosis". J. Biol. Chem. (United States) 276 (24): 21017–21. doi:10.1074/jbc.C100136200. ISSN 0021-9258. PMID 11290735.
- ^ van Slegtenhorst, M; Nellist M, Nagelkerken B, Cheadle J, Snell R, van den Ouweland A, Reuser A, Sampson J, Halley D, van der Sluijs P (Jun. 1998). "Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products". Hum. Mol. Genet. (ENGLAND) 7 (6): 1053–7. doi:10.1093/hmg/7.6.1053. ISSN 0964-6906. PMID 9580671.
- ^ Nellist, Mark; Goedbloed Miriam A, de Winter Christa, Verhaaf Brenda, Jankie Anita, Reuser Arnold J J, van den Ouweland Ans M W, van der Sluijs Peter, Halley Dicky J J (Oct. 2002). "Identification and characterization of the interaction between tuberin and 14-3-3zeta". J. Biol. Chem. (United States) 277 (42): 39417–24. doi:10.1074/jbc.M204802200. ISSN 0021-9258. PMID 12176984.
- ^ Li, Yong; Inoki Ken, Guan Kun-Liang (Sep. 2004). "Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity". Mol. Cell. Biol. (United States) 24 (18): 7965–75. doi:10.1128/MCB.24.18.7965-7975.2004. ISSN 0270-7306. PMC 515062. PMID 15340059. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=515062.
- ^ Mak, Baldwin C; Takemaru Ken-Ichi, Kenerson Heidi L, Moon Randall T, Yeung Raymond S (Feb. 2003). "The tuberin-hamartin complex negatively regulates beta-catenin signaling activity". J. Biol. Chem. (United States) 278 (8): 5947–51. doi:10.1074/jbc.C200473200. ISSN 0021-9258. PMID 12511557.
- ^ Ma, Li; Chen Zhenbang, Erdjument-Bromage Hediye, Tempst Paul, Pandolfi Pier Paolo (Apr. 2005). "Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis". Cell (United States) 121 (2): 179–93. doi:10.1016/j.cell.2005.02.031. ISSN 0092-8674. PMID 15851026.
- ^ Cai, Sheng-Li; Tee Andrew R, Short John D, Bergeron Judith M, Kim Jinhee, Shen Jianjun, Guo Ruifeng, Johnson Charles L, Kiguchi Kaoru, Walker Cheryl Lyn (Apr. 2006). "Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning". J. Cell Biol. (United States) 173 (2): 279–89. doi:10.1083/jcb.200507119. ISSN 0021-9525. PMC 2063818. PMID 16636147. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2063818.
- ^ Cao, Yongheng; Kamioka Yuji, Yokoi Norihide, Kobayashi Toshiyuki, Hino Okio, Onodera Masafumi, Mochizuki Naoki, Nakae Jun (Dec. 2006). "Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway". J. Biol. Chem. (United States) 281 (52): 40242–51. doi:10.1074/jbc.M608116200. ISSN 0021-9258. PMID 17077083.
- ^ Inoki, Ken; Zhu Tianqing, Guan Kun-Liang (Nov. 2003). "TSC2 mediates cellular energy response to control cell growth and survival". Cell (United States) 115 (5): 577–90. doi:10.1016/S0092-8674(03)00929-2. ISSN 0092-8674. PMID 14651849.
- ^ Nellist, Mark; Burgers Peter C, van den Ouweland Ans M W, Halley Dicky J J, Luider Theo M (Aug. 2005). "Phosphorylation and binding partner analysis of the TSC1-TSC2 complex". Biochem. Biophys. Res. Commun. (United States) 333 (3): 818–26. doi:10.1016/j.bbrc.2005.05.175. ISSN 0006-291X. PMID 15963462.
- ^ Goncharova, Elena A; Goncharov Dmitriy A, Spaits Matthew, Noonan Daniel J, Talovskaya Ekaterina, Eszterhas Andrew, Krymskaya Vera P (May. 2006). "Abnormal growth of smooth muscle-like cells in lymphangioleiomyomatosis: Role for tumor suppressor TSC2". Am. J. Respir. Cell Mol. Biol. (United States) 34 (5): 561–72. doi:10.1165/rcmb.2005-0300OC. ISSN 1044-1549. PMC 2644221. PMID 16424383. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2644221.
- ^ Astrinidis, Aristotelis; Senapedis William, Coleman Thomas R, Henske Elizabeth Petri (Dec. 2003). "Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1/cyclin B". J. Biol. Chem. (United States) 278 (51): 51372–9. doi:10.1074/jbc.M303956200. ISSN 0021-9258. PMID 14551205.
- ^ Nellist, M; Verhaaf B, Goedbloed M A, Reuser A J, van den Ouweland A M, Halley D J (Dec. 2001). "TSC2 missense mutations inhibit tuberin phosphorylation and prevent formation of the tuberin-hamartin complex". Hum. Mol. Genet. (England) 10 (25): 2889–98. doi:10.1093/hmg/10.25.2889. ISSN 0964-6906. PMID 11741832.
- ^ Benvenuto, G; Li S, Brown S J, Braverman R, Vass W C, Cheadle J P, Halley D J, Sampson J R, Wienecke R, DeClue J E (Dec. 2000). "The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination". Oncogene (England) 19 (54): 6306–16. doi:10.1038/sj.onc.1204009. ISSN 0950-9232. PMID 11175345.
- ^ Murthy, V; Haddad L A, Smith N, Pinney D, Tyszkowski R, Brown D, Ramesh V (May. 2000). "Similarities and differences in the subcellular localization of hamartin and tuberin in the kidney". Am. J. Physiol. Renal Physiol. (United States) 278 (5): F737–46. ISSN 0363-6127. PMID 10807585.
- ^ Miloloza, A; Rosner M, Nellist M, Halley D, Bernaschek G, Hengstschläger M (Jul. 2000). "The TSC1 gene product, hamartin, negatively regulates cell proliferation". Hum. Mol. Genet. (ENGLAND) 9 (12): 1721–7. doi:10.1093/hmg/9.12.1721. ISSN 0964-6906. PMID 10915759.
- ^ Roux, Philippe P; Ballif Bryan A, Anjum Rana, Gygi Steven P, Blenis John (Sep. 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. (United States) 101 (37): 13489–94. doi:10.1073/pnas.0405659101. ISSN 0027-8424. PMC 518784. PMID 15342917. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=518784.
- ^ Haddad, Luciana A; Smith Nicole, Bowser Mark, Niida Yo, Murthy Vanishree, Gonzalez-Agosti Charo, Ramesh Vijaya (Nov. 2002). "The TSC1 tumor suppressor hamartin interacts with neurofilament-L and possibly functions as a novel integrator of the neuronal cytoskeleton". J. Biol. Chem. (United States) 277 (46): 44180–6. doi:10.1074/jbc.M207211200. ISSN 0021-9258. PMID 12226091.
External links
Further reading
- Hengstschläger M (2002). "Tuberous sclerosis complex genes: from flies to human genetics.". Arch. Dermatol. Res. 293 (8): 383–6. doi:10.1007/s004030100250. PMID 11686512.
- Ramesh V (2004). "Aspects of tuberous sclerosis complex (TSC) protein function in the brain.". Biochem. Soc. Trans. 31 (Pt 3): 579–83. doi:10.1042/BST0310579. PMID 12773159.
- Knowles MA, Hornigold N, Pitt E (2004). "Tuberous sclerosis complex (TSC) gene involvement in sporadic tumours.". Biochem. Soc. Trans. 31 (Pt 3): 597–602. doi:10.1042/BST0310597. PMID 12773163.
- Ellisen LW (2007). "Growth control under stress: mTOR regulation through the REDD1-TSC pathway.". Cell Cycle 4 (11): 1500–02. doi:10.4161/cc.4.11.2139. PMID 16258273.
- Jozwiak J, Jozwiak S (2007). "Giant cells: contradiction to two-hit model of tuber formation?". Cell. Mol. Neurobiol. 27 (2): 251–61. doi:10.1007/s10571-006-9106-0. PMID 16897363.
- Nagase T, Seki N, Ishikawa K, et al. (1997). "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain.". DNA Res. 3 (5): 321–9, 341–54. doi:10.1093/dnares/3.5.321. PMID 9039502.
- van Slegtenhorst M, de Hoogt R, Hermans C, et al. (1997). "Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34.". Science 277 (5327): 805–8. doi:10.1126/science.277.5327.805. PMID 9242607.
- Jones AC, Daniells CE, Snell RG, et al. (1997). "Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis.". Hum. Mol. Genet. 6 (12): 2155–61. doi:10.1093/hmg/6.12.2155. PMID 9328481.
- van Slegtenhorst M, Nellist M, Nagelkerken B, et al. (1998). "Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products.". Hum. Mol. Genet. 7 (6): 1053–7. doi:10.1093/hmg/7.6.1053. PMID 9580671.
- Plank TL, Yeung RS, Henske EP (1998). "Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles.". Cancer Res. 58 (21): 4766–70. PMID 9809973.
- Kwiatkowska J, Jozwiak S, Hall F, et al. (1999). "Comprehensive mutational analysis of the TSC1 gene: observations on frequency of mutation, associated features, and nonpenetrance.". Ann. Hum. Genet. 62 (Pt 4): 277–85. doi:10.1046/j.1469-1809.1998.6240277.x. PMID 9924605.
- van Slegtenhorst M, Verhoef S, Tempelaars A, et al. (1999). "Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation.". J. Med. Genet. 36 (4): 285–9. doi:10.1136/jmg.36.4.285. PMC 1734341. PMID 10227394. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1734341.
- Niida Y, Lawrence-Smith N, Banwell A, et al. (2000). "Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis.". Hum. Mutat. 14 (5): 412–22. doi:10.1002/(SICI)1098-1004(199911)14:5<412::AID-HUMU7>3.0.CO;2-K. PMID 10533067.
- Zhang H, Nanba E, Yamamoto T, et al. (2000). "Mutational analysis of TSC1 and TSC2 genes in Japanese patients with tuberous sclerosis complex.". J. Hum. Genet. 44 (6): 391–6. doi:10.1007/s100380050185. PMID 10570911.
- Nellist M, van Slegtenhorst MA, Goedbloed M, et al. (2000). "Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin.". J. Biol. Chem. 274 (50): 35647–52. doi:10.1074/jbc.274.50.35647. PMID 10585443.
- Yamashita Y, Ono J, Okada S, et al. (2000). "Analysis of all exons of TSC1 and TSC2 genes for germline mutations in Japanese patients with tuberous sclerosis: report of 10 mutations.". Am. J. Med. Genet. 90 (2): 123–6. doi:10.1002/(SICI)1096-8628(20000117)90:2<123::AID-AJMG7>3.0.CO;2-L. PMID 10607950.
- Lamb RF, Roy C, Diefenbach TJ, et al. (2000). "The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho.". Nat. Cell Biol. 2 (5): 281–7. doi:10.1038/35010550. PMID 10806479.
- Miloloza A, Rosner M, Nellist M, et al. (2000). "The TSC1 gene product, hamartin, negatively regulates cell proliferation.". Hum. Mol. Genet. 9 (12): 1721–7. doi:10.1093/hmg/9.12.1721. PMID 10915759.
- Murthy V, Stemmer-Rachamimov AO, Haddad LA, et al. (2001). "Developmental expression of the tuberous sclerosis proteins tuberin and hamartin.". Acta Neuropathol. 101 (3): 202–10. PMID 11307618.
- Catania MG, Mischel PS, Vinters HV (2001). "Hamartin and tuberin interaction with the G2/M cyclin-dependent kinase CDK1 and its regulatory cyclins A and B.". J. Neuropathol. Exp. Neurol. 60 (7): 711–23. PMID 11444800.
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| GTPase activating protein |
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Monomeric
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Heterotrimeric
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Regulator of G protein signalling: RGS1, RGS2, RGS3, RGS4, RGS5, RGS6, RGS7, RGS8, RGS9, RGS10, RGS11, RGS12, RGS13, RGS14, RGS16, RGS17, RGS18, RGS19, RGS20, RGS21
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| Guanine nucleotide exchange factor |
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| Other |
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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