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Tsc1  -  tuberous sclerosis 1

Rattus norvegicus

Synonyms: Hamartin, Tuberous sclerosis 1 protein homolog
 
 
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Disease relevance of Tsc1

 

Psychiatry related information on Tsc1

  • Tuberous sclerosis (TS) is an autosomal dominant disorder in which affected individuals manifest mental retardation, seizures, and a variety of benign and malignant tumors [6].
 

High impact information on Tsc1

  • The phenotype of tuberous sclerosis in humans differs from that of the Eker rat, except for the occurrence of renal tumours [7].
  • We have previously established a new conserved linkage group on rat chromosome 10q and human chromosome 16p13.3, and shown that the Eker mutation is tightly linked to the tuberous sclerosis (Tsc2) gene [7].
  • We now describe a germline mutation in the gene encoding Tsc2 caused by the insertion of an approximately 5 kilobase DNA fragment in the Eker rat, resulting in aberrant RNA expression from the mutant allele [7].
  • Furthermore, loss of a single copy of the Tsc1 gene was sufficient to perturb dendritic spine structure [8].
  • Heterozygous Tsc1 mutant (Tsc1(+/-)) mice developed renal and extra-renal tumors such as hepatic hemangiomas [9].
 

Biological context of Tsc1

 

Anatomical context of Tsc1

 

Associations of Tsc1 with chemical compounds

 

Physical interactions of Tsc1

  • Co-expression of tuberin stabilized hamartin, which is weakly ubiquitinated, in transiently transfected cells [11].
 

Other interactions of Tsc1

 

Analytical, diagnostic and therapeutic context of Tsc1

References

  1. Tuberin is a component of lipid rafts and mediates caveolin-1 localization: role of TSC2 in post-Golgi transport. Jones, K.A., Jiang, X., Yamamoto, Y., Yeung, R.S. Exp. Cell Res. (2004) [Pubmed]
  2. Platelet-derived growth factor-induced p42/44 mitogen-activated protein kinase activation and cellular growth is mediated by reactive oxygen species in the absence of TSC2/tuberin. Finlay, G.A., Thannickal, V.J., Fanburg, B.L., Kwiatkowski, D.J. Cancer Res. (2005) [Pubmed]
  3. Ets protein Elf-1 bidirectionally suppresses transcriptional activities of the tumor suppressor Tsc2 gene and the repair-related Nth1 gene. Honda, S., Kobayashi, T., Kajino, K., Urakami, S., Igawa, M., Hino, O. Mol. Carcinog. (2003) [Pubmed]
  4. Specific induction of hepatocellular adenomas by transplacental administration of ENU in the tsc2 gene mutant (Eker) rat. Fukuda, T., Mitani, H., Tsutsumi, M., Konishi, Y., Hino, O. Int. J. Oncol. (1998) [Pubmed]
  5. Molecular genetics of renal carcinogenesis. Walker, C. Toxicologic pathology. (1998) [Pubmed]
  6. Expression of the tuberous sclerosis 2 gene product, tuberin, in adult and developing nervous system tissues. Geist, R.T., Reddy, A.J., Zhang, J., Gutmann, D.H. Neurobiol. Dis. (1996) [Pubmed]
  7. A germline insertion in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancer. Kobayashi, T., Hirayama, Y., Kobayashi, E., Kubo, Y., Hino, O. Nat. Genet. (1995) [Pubmed]
  8. Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2. Tavazoie, S.F., Alvarez, V.A., Ridenour, D.A., Kwiatkowski, D.J., Sabatini, B.L. Nat. Neurosci. (2005) [Pubmed]
  9. A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice. Kobayashi, T., Minowa, O., Sugitani, Y., Takai, S., Mitani, H., Kobayashi, E., Noda, T., Hino, O. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  10. Regulation of microtubule-dependent protein transport by the TSC2/mammalian target of rapamycin pathway. Jiang, X., Yeung, R.S. Cancer Res. (2006) [Pubmed]
  11. The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination. 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. Oncogene (2000) [Pubmed]
  12. Absence of allelic loss in cytomegalic neurons of cortical tuber in the Eker rat model of tuberous sclerosis. Mizuguchi, M., Mori, M., Nozaki, Y., Momoi, M.Y., Itoh, M., Takashima, S., Hino, O. Acta Neuropathol. (2004) [Pubmed]
  13. A new Western blotting method using polymer immunocomplexes: detection of Tsc1 and Tsc2 expression in various cultured cell lines. Fukuda, T., Tani, Y., Kobayashi, T., Hirayama, Y., Hino, O. Anal. Biochem. (2000) [Pubmed]
  14. Distribution of Tsc1 protein detected by immunohistochemistry in various normal rat tissues and the renal carcinomas of Eker rat: detection of limited colocalization with Tsc1 and Tsc2 gene products in vivo. Fukuda, T., Kobayashi, T., Momose, S., Yasui, H., Hino, O. Lab. Invest. (2000) [Pubmed]
  15. Isolation and characterization of a rat homologue of the human tuberous sclerosis 1 gene (Tsc1) and analysis of its mutations in rat renal carcinomas. Satake, N., Kobayashi, T., Kobayashi, E., Izumi, K., Hino, O. Cancer Res. (1999) [Pubmed]
  16. Identification of the coding sequences responsible for Tsc2-mediated tumor suppression using a transgenic rat system. Momose, S., Kobayashi, T., Mitani, H., Hirabayashi, M., Ito, K., Ueda, M., Nabeshima, Y., Hino, O. Hum. Mol. Genet. (2002) [Pubmed]
  17. Spatial memory formation and memory-enhancing effect of glucose involves activation of the tuberous sclerosis complex-Mammalian target of rapamycin pathway. Dash, P.K., Orsi, S.A., Moore, A.N. J. Neurosci. (2006) [Pubmed]
  18. Activated mammalian target of rapamycin pathway in the pathogenesis of tuberous sclerosis complex renal tumors. Kenerson, H.L., Aicher, L.D., True, L.D., Yeung, R.S. Cancer Res. (2002) [Pubmed]
  19. Transgenic rescue from embryonic lethality and renal carcinogenesis in the Eker rat model by introduction of a wild-type Tsc2 gene. Kobayashi, T., Mitani, H., Takahashi, R., Hirabayashi, M., Ueda, M., Tamura, H., Hino, O. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  20. Biallelic mutations of the Tsc2 gene in chemically induced rat renal cell carcinoma. Satake, N., Urakami, S., Hirayama, Y., Izumi, K., Hino, O. Int. J. Cancer (1998) [Pubmed]
  21. Inactivation of the cyclin-dependent kinase inhibitor p27 upon loss of the tuberous sclerosis complex gene-2. Soucek, T., Yeung, R.S., Hengstschläger, M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  22. Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles. Plank, T.L., Yeung, R.S., Henske, E.P. Cancer Res. (1998) [Pubmed]
  23. Hamartin expression and interaction with tuberin in tumor cell lines and primary cultures. Catania, M.G., Johnson, M.W., Liau, L.M., Kremen, T.J., deVellis, J.S., Vinters, H.V. J. Neurosci. Res. (2001) [Pubmed]
  24. Distribution of Tsc2 protein in various normal rat tissues and renal tumours of Tsc2 mutant (Eker) rat detected by immunohistochemistry. Fukuda, T., Kobayashi, T., Yasui, H., Tsutsumi, M., Konishi, Y., Hino, O. Virchows Arch. (1999) [Pubmed]
 
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