TSC2

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Tuberous sclerosis 2
Identifiers
Symbols TSC2 ; LAM; TSC4
External IDs OMIM191092 MGI102548 HomoloGene462 GeneCards: TSC2 Gene
RNA expression pattern
PBB GE TSC2 215735 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 7249 22084
Ensembl ENSG00000103197 ENSMUSG00000002496
UniProt P49815 Q3UGI8
RefSeq (mRNA) NM_000548 NM_001039363
RefSeq (protein) NP_000539 NP_001034452
Location (UCSC) Chr 16:
2.1 – 2.14 Mb
Chr 17:
24.6 – 24.63 Mb
PubMed search [1] [2]

Tuberin also known as tuberous sclerosis 2 is a protein that in humans is encoded by the TSC2 gene.

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. 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]

Interactions[edit]

TSC2 has been shown to interact with:

See also[edit]


References[edit]

  1. ^ "Entrez Gene: TSC2 tuberous sclerosis 2". 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ 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. 
  13. ^ 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. 
  14. ^ 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. 
  15. ^ 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. 
  16. ^ 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. 
  17. ^ 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. 
  18. ^ 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. 
  19. ^ 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. 
  20. ^ 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. 
  21. ^ 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. 
  22. ^ 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. 
  23. ^ 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. 

Further reading[edit]

External links[edit]