Tuberous sclerosis: From tubers to mTOR

Annals of Human Genetics

Volumn 67, Issue 1, 2003, Pages 87-96

  Kwiatkowski, David J ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; RAPAMYCIN; TARGET OF RAPAMYCIN KINASE; TUBERIN; MAMMALIAN TARGET OF RAPAMYCIN; PROTEIN; PROTEIN KINASE; REPRESSOR PROTEIN; TUBEROUS SCLEROSIS COMPLEX 1 PROTEIN; TUMOR SUPPRESSOR PROTEIN;

AUTOSOMAL DOMINANT DISORDER; CELL SIZE; DROSOPHILA; EPISTASIS; GENE DELETION; GENE DUPLICATION; GENE INSERTION; GENETIC CODE; GENETIC IDENTIFICATION; HAMARTOMA; HUMAN; MISSENSE MUTATION; NONHUMAN; NONSENSE MUTATION; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; RETROSPECTIVE STUDY; REVIEW; SIGNAL TRANSDUCTION; TUBEROUS SCLEROSIS; ANIMAL; GENETICS; METABOLISM; PATHOPHYSIOLOGY;

ANIMALS; PROTEIN KINASES; PROTEINS; REPRESSOR PROTEINS; SIGNAL TRANSDUCTION; TUBEROUS SCLEROSIS; TUMOR SUPPRESSOR PROTEINS;

EID: 0041758428     PISSN: 00034800     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1469-1809.2003.00012.x     Document Type: Review

References (58)

1. Al-Saleem, T., Wessner, L. L., Scheithauer, B. W., Patterson, K., Roach, E. S., Dreyer, S. J., Fujikawa, K., Bjornsson, J., Bernstein, J. & Henske, E. P. (1998). Malignant tumors of the kidney, brain, and soft tissues in children and young adults with the tuberous sclerosis complex. Cancer 83, 2208-16.
2. 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. (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 19, 6306-16.
3. Blume-Jensen, P. & Hunter, T. (2001). Oncogenic kinase signalling. Nature 411, 355-65.
4. Cheadle, J. P., Reeve, M. P., Sampson, J. R. & Kwiatkowski, D. J. (2000). Molecular genetic advances in tuberous sclerosis. Hum Genet 107, 97-114.
5. The European Chromosome 16 Tuberous Sclerosis Consortium. (1993). Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 75, 1305-1315.
6. Cook, J. A., Oliver, K., Mueller, R. F. & Sampson, J. (1996). A cross sectional study of renal involvement in tuberous sclerosis. J Med Genet 33, 480-4.
7. Costello, L. C., Hartman, T. E. & Ryu, J. H. (2000). High frequency of pulmonary lymphangioleiomyomatosis in women with tuberous sclerosis complex. Mayo Clin Proc 75, 591-4.
8. Dabora, S. L., Jozwiak, S., Franz, D. N., Roberts, P. S., Nieto, A., Chung, J., Choy, Y. S., Reeve, M. P., Thiele, E., Egelhoff, J. C., Kasprzyk-Obara, J., Domanska-Pakiela, D. & Kwiatkowski, D. J. (2001). Mutational Analysis in a Cohort of 224 Tuberous Sclerosis Patients Indicates Increased Severity of TSC2, Compared with TSC1, Disease in Multiple Organs. Am J Hum Genet 68, 64-80.
9. Dan, H. C., Sun, M., Yang, L., Feldman, R. I., Sui, X. M., Yeung, R. S., Halley, D. J., Nicosia, S. V., Pledger, W. J. & Cheng, J. Q. (2002). PI3K/AKT pathway regulates TSC tumor suppressor complex by phosphorylation of tuberin. J Biol Chem 277, 35364-70.
10. Dennis, P. B., Jaeschke, A., Saitoh, M., Fowler, B., Kozma, S. C. & Thomas, G. (2001). Mammalian TOR: a homeostatic ATP sensor. Science 294, 1102-5.
11. Eker, R., Mossige, J., Johannessen, J. V. & Aars, H. (1981). Hereditary renal adenomas and adenocarcinomas in rats. Diagn Histopath 4, 99-110.
12. Fang, Y., Vilella-Bach, M., Bachmann, R., Flanigan, A. & Chen, J. (2001). Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science 294, 1942-5.
13. Franz, D. N., Brody, A., Meyer, C., Leonard, J., Chuck, G., Dabora, S., Sethuraman, G., Colby, T. V., Kwiatkowski, D. J. & McCormack, F. X. (2001). Mutational and Radiographic Analysis of Pulmonary Disease Consistent with Lymphangioleiomyomatosis and Micronodular Pneumocyte Hyperplasia in Women with Tuberous Sclerosis. Am J Respir Crit Care Med 164, 661-668.
14. Gao, X. & Pan, D. (2001). TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes Dev 15, 1383-92.
15. Gao, X., Zhang, Y., Arrazola, P., Hino, O., Kobayashi, T., Yeung, R. S., Ru, B. & Pan, D. (2002). Tsc tumour suppressor proteins antagonize amino-acid TOR signalling. Nat Cell Biol in press.
16. Gingras, A. C., Raught, B. & Sonenberg, N. (2001). Regulation of translation initiation by FRAP/mTOR. Genes Dev 15, 807-26.
17. Gomez, M., Sampson, J. & Whittemore, V. (1999). The tuberous sclerosis complex. Oxford, England: Oxford University Press.
18. Goncharova, E. A., Goncharov, D. A., Eszterhas, A., Hunter,D. S., Glassberg, M. K., Yeung, R. S., Walker, C. L., Noonan, D., Kwiatkowski, D. J., Chou, M. M., Panettieri, R. A., Jr. & Krymskaya, V. P. (2002). Tuberin regulates p70 S6 kinase activation and ribosomal protein S6 phosphorylation: a role for the TSC2 tumor suppressor gene in pulmonary lymphangioleiomyomatosis (LAM). J Biol Chem 277, 30958-67.
19. Hara, K., Maruki, Y., Long, X., Yoshino, K., Oshiro, N., Hidayat, S., Tokunaga, C., Avruch, J. & Yonezawa, K. (2002). Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 110, 177-89.
20. Hara, K., Yonezawa, K., Weng, Q. P., Kozlowski, M. T., Belham, C. & Avruch, J. (1998). Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J Biol Chem 273, 14484-94.
21. Henry, K. W., Yuan, X., Koszewski, N. J., Onda, H., Kwiatkowski, D. J. & Noonan, D. J. (1998). Tuberous sclerosis gene 2 product modulates transcription mediated by steroid hormone receptor family members. J Biol Chem 273, 20535-20539.
22. Henske, E. P., Scheithauer, B. W., Short, M. P., Wollmann, R., Nahmias, J., Hornigold, N., van Slegtenhorst, M., Welsh,C. T. & Kwiatkowski, D. J. (1996). Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions. Am J Hum Genet 59, 400-6.
23. Hodges, A. K., Li, S., Maynard, J., Parry, L., Braverman, R., Cheadle, J. P., DeClue, J. E. & Sampson, J. R. (2001). Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin. Hum Mol Genet 10, 2899-2905.
24. Inoki, K., Li, Y., Zhu, T., Wu, J. & Guan, K. L. (2002). TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol in press.
25. Ito, N. & Rubin, G. M. (1999). gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle. Cell 96, 529-39.
26. Jiang, Y. & Broach, J. R. (1999). Tor proteins and protein phosphatase 2A reciprocally regulate Tap42 in controlling cell growth in yeast. Embo J 18, 2782-92.
27. Jones, A. C., Shyamsundar, M. M., Thomas, M. W., Maynard, J., Idziaszczyk, S., Tomkins, S., Sampson, J. R. & Cheadle, J. P. (1999). Comprehensive Mutation Analysis of TSC1 and TSC2-and Phenotypic Correlations in 150 Families with Tuberous Sclerosis. Am J Hum Genet 64, 1305-1315.
28. Kim, D. H., Sarbassov dos, D., Ali, S. M., King, J. E., Latek, R. R., Erdjument-Bromage, H., Tempst, P. & Sabatini, D. M. (2002). mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110, 163-75.
29. Kleymenova, E., Ibraghimov-Beskrovnaya, O., Kugoh, H., Everitt, J., Xu, H., Kiguchi, K., Landes, G., Harris, P. & Walker, C. (2001). Tuberin-dependent membrane localization of polycystin-1: a functional link between polycystic kidney disease and the TSC2 tumor suppressor gene. Mol Cell 7, 823-32.
30. Kobayashi, T., Minowa, O., Kuno, J., Mitani, H., Hino, O. & Noda, T. (1999). Renal carcinogenesis, hepatic hemangiomatosis, and embryonic lethality caused by a germ-line Tsc2 mutation in mice. Cancer Res 59, 1206-11.
31. Kobayashi, T., Minowa, O., Sugitani, Y., Takai, S., Mitani, H., Kobayashi, E., Noda, T. & Hino, O. (2001). 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. Proc Natl Acad Sci USA 98, 8762-7.
32. Kugoh, H., Kleymenova, E. & Walker, C. L. (2002). Retention of membrane-localized beta-catenin in cells lacking functional polycystin-1 and tuberin. Mol Carcinog 33, 131-6.
33. Kwiatkowski, D. J., Zhang, H., Bandura, J. L., Heiberger, K. M., Glogauer, M., el-Hashemite, N. & Onda, H. (2002). A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells. Hum Mol Genet 11, 525-34.
34. Lamb, R. F., Roy, C., Diefenbach, T. J., Vinters, H. V., Johnson, M. W., Jay, D. G. & Hall, A. (2000). The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho. Nat Cell Biol 2, 281-287.
35. Lazaris-Karatzas, A., Montine, K. S. & Sonenberg, N. (1990). Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5′ cap. Nature 345, 544-7.
36. Lou, D., Griffith, N. & Noonan, D. J. (2001). The tuberous sclerosis 2 gene product can localize to nuclei in a phosphorylation-dependent manner. Mol Cell Biol Res Commun 4, 374-80.
37. Manning, B. D., Tee, A. R., Logsdon, M. N., Blenis, J. & Cantley, L. C. (2002). Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol Cell 10, 151-62.
38. Miloloza, A., Rosner, M., Nellist, M., Halley, D., Bernaschek, G. & Hengstschlager, M. (2000). The TSC1 gene product, hamartin, negatively regulates cell proliferation. Hum Mol Genet 9, 1721-7.
39. Nellist, M., Verhaaf, B., Goedbloed, M. A., Reuser, A. J., van Den Ouweland, A. M. & Halley, D. J. (2001). TSC2 missense mutations inhibit tuberin phosphorylation and prevent formation of the tuberin-hamartin complex. Hum Mol Genet 10, 2889-2898.
40. Niida, Y., Stemmer-Rachamimov, A. O., Logrip, M., Tapon, D., Perez, R., Kwiatkowski, D. J., Sims, K., MacCollin, M., Louis, D. N. & Ramesh, V. (2001). Survey of somatic mutations in tuberous sclerosis complex (TSC) hamartomas suggests different genetic mechanisms for pathogenesis of TSC lesions. Am J Hum Genet 69, 493-503.
41. Noonan, D. J., Lou, D., Griffith, N. & Vanaman, T. C. (2002). A calmodulin binding site in the tuberous sclerosis 2 gene product is essential for regulation of transcription events and is altered by mutations linked to tuberous sclerosis and lymphangioleiomyomatosis. Arch Biochem Biophys 398, 132-40.
42. Onda, H., Crino, P, B., Zhang, H., Murphey, R. D., Rastelli, L., Rothberg, B. E. G. & Kwiatkowski, D. J. (2002). Tsc2 null murine neuroepithelial cells are a model for human tuber giant cells, and show activation of an mTOR pathway. Mol Cell Neurosc in press.
43. Onda, H., Lueck, A., Marks, P. W., Warren, H. B. & Kwiatkowski, D. J. (1999). Tsc2(+/-) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background. J Clin Invest 104, 687-95.
44. Peterson, R. T., Desai, B. N., Hardwick, J. S. & Schreiber, S. L. (1999). Protein phosphatase 2A interacts with the 70-kDa S6 kinase and is activated by inhibition of FKBP12-rapamycinassociated protein. Proc Natl Acad Sci USA 96, 4438-42.
45. Plank, T. L., Yeung, R. S. & Henske, E. P. (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, 4766-70.
46. Potter, C. J., Huang, H. & Xu, T. (2001). Drosophila tsc1 functions with tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell 105, 357-68.
47. Potter, C. J., Pedraza, L. G. & Xu, T. (2002). Akt regulates growth by directly phosphorylating Tsc2. Nat Cell Biol 4, 658-65.
48. Roach, E. S., Gomez, M. R. & Northrup, H. (1998). Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. J Child Neurol 13, 624-8.
49. Soucek, T., Rosner, M., Miloloza, A., Kubista, M., Cheadle, J. P., Sampson, J. R. & Hengstschlager, M. (2001). Tuberous sclerosis causing mutants of the TSC2 gene product affect proliferation and p27 expression. Oncogene 20, 4904-9.
50. Soucek, T., Yeung, R. S. & Hengstschlager, M. (1998). Inactivation of the cyclin-dependent kinase inhibitor p27 upon loss of the tuberous sclerosis complex gene-2. Proc Natl Acad Sci USA 95, 15653-8.
51. Tapon, N., Ito, N., Dickson, B. J., Treisman, J. E. & Hariharan, I. K. (2001). The drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell 105, 345-55.
52. Tee, A. R., Fingar, D. C., Manning, B. D., Kwiatkowski, D. J., Cantley, L. C. & Blenis, J. (2002). Tuberous Sclerosis Complex-1 and 2 gene products function together to inhibit mamamalian toarget of Rapamycin-(mTOR) mediated downstream signalling. Proc Natl Acad Sci USA 99, 13571-6.
53. Uhlmann, E. J., Wong, M., Baldwin, R. L., Bajenaru, M. L., Onda, H., Kwiatkowski, D. J., Yamada, K. & Gutmann, D. H. (2002). Astrocyte-specific TSC1 conditional knockout mice exhibit abnormal neuronal organization and seizures. Ann Neurol 52, 285-96.
54. van Slegtenhorst, M., de Hoogt, R., Hermans, C., Nellist, M., Janssen, B., Verhoef, S., Lindhout, D., van den Ouweland, A., Halley, D., Young, J., Burley, M., Jeremiah, S., Woodward, K., Nahmias, J., Fox, M., Ekong, R., Osborne, J., Wolfe, J., Povey, S., Snell, R. G., Cheadle, J. P., Jones, A. C., Tachataki, M., Ravine, D. & Kwiatkowski, D. J. (1997). Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 277, 805-8.
55. 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. (1998). Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet 7, 1053-1058.
56. Wienecke, R., Konig, A. & DeClue, J. E. (1995). Identification of tuberin, the tuberous sclerosis-2 product. Tuberin possesses specific Rap 1 GAP activity. J Biol Chem 270, 16409-14.
57. Xiao, G. H., Shoarinejad, F., Jin, F., Golemis, E. A. & Yeung, R. S. (1997). The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis. J Biol Chem 272, 6097-100.
58. Yeung, R. S., Katsetos, C. D. & Klein-Szanto, A. (1997). Subependymal astrocytic hamartomas in the Eker rat model of tuberous sclerosis. Am J Pathol 151, 1477-86.