Hamartin and tuberin: Working together for tumour suppression

International Journal of Cancer

Volumn 118, Issue 1, 2006, Pages 1-5

  Jozwiak, Jaroslaw ^a  

^a MEDICAL UNIVERSITY OF WARSAW   (Poland)

Author keywords

Hamartin; mTOR; Tuberin

Indexed keywords

CYCLIN DEPENDENT KINASE 1; DESMIN; ESTROGEN RECEPTOR ALPHA; GUANINE NUCLEOTIDE BINDING PROTEIN; GUANOSINE TRIPHOSPHATASE; HAMARTIN; HYPOXIA INDUCIBLE FACTOR 1; MAMMALIAN TARGET OF RAPAMYCIN; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; NOCODAZOLE; RAC1 PROTEIN; RAS PROTEIN; RHEB PROTEIN; S6 KINASE; TUBERIN; UNCLASSIFIED DRUG;

BIOLOGICAL ACTIVITY; CANCER INHIBITION; CELL PROLIFERATION; CELL STRAIN HEK293; CONTROLLED STUDY; ENDOSOME; ENZYME ACTIVITY; HAMARTOMA; HORMONE RECEPTOR INTERACTION; HUMAN; HUMAN CELL; LYMPHANGIOLEIOMYOMATOSIS; MATRIX ASSISTED LASER DESORPTION IONIZATION TIME OF FLIGHT MASS SPECTROMETRY; MESSENGER RNA SYNTHESIS; POINT MUTATION; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SHORT SURVEY; SIGNAL TRANSDUCTION; TUBEROUS SCLEROSIS; TUMOR SUPPRESSOR GENE; UBIQUITINATION;

CELL TRANSFORMATION, NEOPLASTIC; GROWTH SUBSTANCES; HAMARTOMA; HUMANS; MONOMERIC GTP-BINDING PROTEINS; NEUROPEPTIDES; PHOSPHORYLATION; PHOSPHOTRANSFERASES; TUMOR SUPPRESSOR PROTEINS;

EID: 27944450100     PISSN: 00207136     EISSN: None     Source Type: Journal    
DOI: 10.1002/ijc.21542     Document Type: Short Survey

References (42)

1. 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, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 1997;277:805-8.
2. European Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. The European Chromosome 16 Tuberous Sclerosis Consortium. Cell 1993;75:1305-15.
3. Nellist M, van Slegtenhorst MA, Goedbloed M, van den Ouweland AM, Halley DJ, van der Sluijs P. Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin. J Biol Chem 1999;274:35647-52.
4. Jozwiak J, Jozwiak S. Giant Cells: contradiction to two-hit model of tuber formation? Cell Mol Neurobiol 2005;25:793-803.
5. Yamagata K, Sanders LK, Kaufmann WE, Yee W, Barnes CA, Nathans D, Worley PF. Rheb, a growth factor- and synaptic activity-regulated gene, encodes a novel Ras-related protein. J Biol Chem 1994;269:16333-9.
6. Mach KE, Furge KA, Albright CF. Loss of Rhb1, a Rheb-related GTPase in fission yeast, causes growth arrest with a terminal phenotype similar to that caused by nitrogen starvation. Genetics 2000;155:611-22.
7. Yang W, Tabancay AP, Jr., Urano J, Tamanoi F. Failure to farnesylate Rheb protein contributes to the enrichment of G0/G1 phase cells in the Schizosaccharomyces pombe farnesyltransferase mutant. Mol Microbiol 2001;41:1339-47.
8. Castro AF, Rebhun JF, Clark GJ, Quilliam LA. Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner. J Biol Chem 2003;278:32493-6.
9. Inoki K, Zhu T, Guan KL. TSC2 mediates cellular energy response to control cell growth and survival. Cell 2003;115:577-90.
10. Brugarolas J, Lei K, Hurley RL, Manning BD, Reiling JH, Hafen E, Witters LA, Ellisen LW, Kaelin WG, Jr. Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev 2004;18:2893-904.
11. Dabora SL, Jozwiak S, Franz DN, Roberts PS, Nieto A, Chung J, Choy YS, Reeve MP, Thiele E, Egelhoff JC, Kasprzyk-Obara J, Domanska-Pakiela D, et al. 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 2001;68:64-80.
12. Tee AR, Manning BD, Roux PP, Cantley LC, Blenis J. Tuberous sclerosis complex gene products, tuberin and hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr Biol 2003;13:1259-68.
13. Fryer AE, Chalmers A, Connor JM, Fraser I, Povey S, Yates AD, Yates JR, Osborne JP. Evidence that the gene for tuberous sclerosis is on chromosome 9. Lancet 1987;1:659-61.
14. Plank TL, Logginidou H, Klein-Szanto A, Henske EP. The expression of hamartin, the product of the TSC1 gene, in normal human tissues and in TSC1- and TSC2-linked angiomyolipomas. Mod Pathol 1999; 12:539-45.
15. Johnson MW, Kerfoot C, Bushnell T, Li M, Vinters HV. Hamartin and tuberin expression in human tissues. Mod Pathol 2001;14:202-10.
16. Jansen FE, Notenboom RG, Nellist M, Goedbloed MA, Halley DJ, de Graan PN, van Nieuwenhuizen O. Differential localization of hamartin and tuberin and increased S6 phosphorylation in a tuber. Neurology 2004;63:1293-95.
17. 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. Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet 1998;7:1053-7.
18. Nellist M, Verhaaf B, Goedbloed MA, Reuser AJ, van den Ouweland AM, Halley DJ. TSC2 missense mutations inhibit tuberin phosphorylation and prevent formation of the tuberin-hamartin complex. Hum Mol Genet 2001;10:2889-98.
19. Lamb RF, Roy C, Diefenbach TJ, Vinters HV, Johnson MW, Jay DG, Hall A. The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho. Nat Cell Biol 2000;2:281-7.
20. Goncharova E, Goncharov D, Noonan D, Krymskaya VP. TSC2 modulates actin cytoskeleton and focal adhesion through TSC1-binding domain and the Rac1 GTPase. J Cell Biol 2004;167:1171-82.
21. Haddad LA, Smith N, Bowser M, Niida Y, Murthy V, Gonzalez-Agosti C, Ramesh V. The TSC1 tumor suppressor hamartin interacts with neurofilament-L and possibly functions as a novel integrator of the neuronal cytoskeleton. J Biol Chem 2002;277:44180-6.
22. Astrinidis A, Senapedis W, Coleman TR, Henske EP. 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 2003;278:51372-9.
23. Nellist M, Burgers PC, van den Ouweland AM, Halley DJ, Luider TM. Phosphorylation and binding partner analysis of the TSC1-TSC2 complex. Biochem Biophys Res Commun 2005;333:818-26.
24. Inoki K, Li Y, Xu T, Guan KL. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev 2003; 17:1829-34.
25. Wienecke R, Konig A, DeClue JE. Identification of tuberin, the tuberous sclerosis-2 product. Tuberin possesses specific Rap1GAP activity. J Biol Chem 1995;270:16409-14.
26. Xiao GH, Shoarinejad F, Jin F, Golemis EA, Yeung RS. The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis. J Biol Chem 1997;272:6097-100.
27. Maheshwar MM, Cheadle JP, Jones AC, Myring J, Fryer AE, Harris PC, Sampson JR. The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis. Hum Mol Genet 1997;6:1991-6.
28. Li Y, Inoki K, Guan KL. Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity. Mol Cell Biol 2004;24:7965-75.
29. Momose S, Kobayashi T, Mitani H, Hirabayashi M, Ito K, Ueda M, Nabeshima Y, Hino O. Identification of the coding sequences responsible for Tsc2-mediated tumor suppression using a transgenic rat system. Hum Mol Genet 2002;11:2997-3006.
30. Benvenuto G, Li S, Brown SJ, Braverman R, Vass WC, Cheadle JP, Halley DJ, Sampson JR, Wienecke R, DeClue JE. 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 2000;19:6306-16.
31. Mayer K, Goedbloed M, van Zijl K, Nellist M, Rott HD. Characterisation of a novel TSC2 missense mutation in the GAP related domain associated with minimal clinical manifestations of tuberous sclerosis. J Med Genet 2004;41:e64.
32. Noonan DJ, Lou D, Griffith N, Vanaman TC. 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 2002;398:132-40.
33. York B, Lou D, Panettieri RA, Jr., Krymskaya VP, Vanaman TC, Noonan DJ. Cross-talk between tuberin, calmodulin, and estrogen signaling pathways. FASEB J 2005;19:1202-4.
34. Jones KA, Jiang X, Yamamoto Y, Yeung RS. Tuberin is a component of lipid rafts and mediates caveolin-1 localization: role of TSC2 in post-Golgi transport. Exp Cell Res 2004;295:512-24.
35. Dan HC, Sun M, Yang L, Feldman RI, Sui XM, Ou CC, Nellist M, Yeung RS, Halley DJ, Nicosia SV, Pledger WJ, Cheng JQ. Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin. J Biol Chem 2002;277:35364-70.
36. Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J. Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Proc Natl Acad Sci USA 2004;101:13489-94.
37. Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP. Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell 2005;121:179-93.
38. Corradetti MN, Inoki K, Bardeesy N, DePinho RA, Guan KL. Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome. Genes Dev 2004;18:1533-8.
39. Inoki K, Zhu T, Guan KL. TSC2 mediates cellular energy response to control cell growth and survival. Cell 2003;115:577-90.
40. Brugarolas J, Lei K, Hurley RL, Manning BD, Reiling JH, Hafen E, Witters LA, Ellisen LW, Kaelin WG, Jr. Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev 2004;18:2893-904.
41. Li Y, Inoki K, Vacratsis P, Guan KL. The p38 and MK2 kinase cascade phosphorylates tuberin, the tuberous sclerosis 2 gene product, and enhances its interaction with 14-3-3. J Biol Chem 2003;278: 13663-71.
42. Shumway SD, Li Y, Xiong Y. 14-3-3beta binds to and negatively regulates the tuberous sclerosis complex 2 (TSC2) tumor suppressor gene product, tuberin. J Biol Chem 2003;278:2089-92.