Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
권호 표지
DOI QR코드

DOI QR Code

Interaction of FERM Domain of Tumor Suppressor, Merlin to its C-terminal Domain.

종양 억제 인자, Merlin의 FERM 도메인과 C-말단 도메인간의 결합

  • Oh, Jeong-Il (School of Life Science and Biotechnology, Kyungpook National University) ;
  • Kang, Beom-Sik (Department of Microbiology, Pusan National University)
  • 강범식 (경북대학교 자연과학대학 생명공학부) ;
  • 오정일 (부산대학교 자연과학대학 미생물학과)
  • Published : 2007.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

A tumor suppressor, merlin is a member of ERM family proteins. It consists of N-terminal FERM domain, ${\alpha}-helical$ region, and C-terminal domain. Alternative splicing of merlin's mRNA generates two isotypes of merlin. Isotype I, which has exon17 at the C-terminus instead of exon16 in isotype II, is known to have tumor suppressor activity. Like other ERM proteins, the C-terminal domain of merlin isotype I interacts to its FERM domain. That of isotype II, however, was reported not to bind FERM domain despite the large common part of C-terminal domain, which possibly binds FERM domain. Here, we show the binding of FERM domain to both C-terminal domains of merlin's two isotypes by isothermal titration calorimetry. These results support that merlin isotype II also can form a closed conformation or a multimer by intramolecular or intermolecular interactions using their FERM domain and C-terminal domain.

Keywords

References

  1. Baser, M. E., D. G. Evans and D. H. Gutmann. 2003. Neurofibromatosis 2. Curr. Opin. Neurol. 16, 27-33 https://doi.org/10.1097/00019052-200302000-00004
  2. Berryman, M., R. Gary and A. Bretscher. 1995. Ezrin oligomers are major cytoskeletal components of placental microvilli: a proposal for their involvement in cortical morphogenesis. J. Cell Biol. 131, 1231-1242 https://doi.org/10.1083/jcb.131.5.1231
  3. Bianchi, A. B., T. Gara, V. Ramesh, J. Gao, A. J. KleinSzanto, F. Morin, A. G. Menon, J. A. Trofatter, J. F. Gusella and B. R. Seizinger. 1994. Mutations in transcript isoforrns of the neurofibromatosis 2 gene in multiple human tumour types. Nat. Genet. 6, 185-192 https://doi.org/10.1038/ng0294-185
  4. Evans, D. G., M. Sainio and M. E. Baser. 2000. Neurofibromatosis type 2. J. Med. Genet. 37, 897-904 https://doi.org/10.1136/jmg.37.12.897
  5. Gary, R. and A. Bretscher. 1993. Heterotypic and homotypic associations between ezrin and moesin, two putative membrane-cytoskeletal linking proteins. Proc. Natl. Acad. Sci. USA 90, 10846-10850 https://doi.org/10.1073/pnas.90.22.10846
  6. Gutman, D. H. 1997. Molecular insights into neurofibromatosis 2. Neurobiol. Dis. 3, 247-261 https://doi.org/10.1006/nbdi.1997.0128
  7. Hara, T., A. B. Bianchi, B. R. Seizinger and N. Kley. 1994. Molecular cloning and characterization of alternatively spliced transcripts of the mouse neurofibromatosis 2 gene. Cancer Res. 54, 330-335
  8. Heiska, L., K. Alfthan, M. Cronholm, P. Vilja, A. Vaheri and O. Carpen. 1998. Association of ezrin with intercellular adhesion molecule-1 and -2 (ICAM-1 and ICAM-2). Regulation by phosphatidylinositol 4, 5-bisphosphate. J. Biol. Chem. 273, 21893-900 https://doi.org/10.1074/jbc.273.34.21893
  9. Jannatipour, M., P. Dion, S. Khan, H. Jindal, X. Fan, J. Laqaniere, A. H. Chishti and G. A. Rouleau. 2001. Schwannomin isoform-1 interacts with syntenin via PDZ domains. J. Biol. Chem. 276, 33093-33100 https://doi.org/10.1074/jbc.M105792200
  10. Koo, T. H, J. J. Lee, E. M. Kim, K. W. Kim, H D. Kim and J. H. Lee. 2002. Syntenin is overexpressed and promotes cell migration in metastatic human breast and gastric cell lines. Oncogene 21, 4080-4088 https://doi.org/10.1038/sj.onc.1205514
  11. Li, Y., G. Bollag, R. Clark, J. Stevens, L. Conroy, D. Fults, K Ward, E. Friedman, W. Samowitz and M. Robertson. 1992. Somatic mutations in the neurofibromatosis 1 gene in human tumors. Cell 69, 275-281 https://doi.org/10.1016/0092-8674(92)90408-5
  12. Lutchman, M. and G. A. Rouleu. 1996. Neurofibromatosis type 2: a new mechanism of tumor suppression. Trends Neurosci. 19, 373-377 https://doi.org/10.1016/S0166-2236(96)10044-8
  13. Maeda, M., T. Matsui, M. Imamura, S. Tsukita and S. Tsukita. 1999. Expression level, subcellular distribution and rho-GDI binding affinity of merlin in comparison with Ezrin/Radixin/Moesin proteins. Oncogene 18, 4788-4797 https://doi.org/10.1038/sj.onc.1202871
  14. Murthy, A., C. Gonzalez-Agosti, E, Cordero, D. Pinney, C. Candia, F. Solomon, J. Gusella and V. Ramesh. 1998. NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common interactor for merlin and ERM (MERM) proteins. J. Biol. Chem. 273, 1273-1276 https://doi.org/10.1074/jbc.273.3.1273
  15. Pestonjamasp, K, M. R. Amieva, C. P. Strassel, W. M. Nauseef, H. Furthmayr and E. J. Luna. 1995. Moesin, ezrin, and p205 are actin-binding proteins associated with neutrophil plasma membranes. Mol. Biol. Cell 6, 247-259 https://doi.org/10.1091/mbc.6.3.247
  16. Rouleau, G. A, P. Merel, M. Lutchman, M. Sanson, J. Zucman, C. Marineau, K Hoang-Xuan, S. Demczuk, C. Desmaze and B. Plouqastel. 1993. Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature 363, 515-521 https://doi.org/10.1038/363515a0
  17. Sheffield, P., S. Garrard and Z. Derewenda. 1999. Overcoming expression and purification problems of RhoGDI using a family of 'Parallel' expression vectors. Protein Expr. Purif. 15, 34-39 https://doi.org/10.1006/prep.1998.1003
  18. Sherman, L., H. M. Xu, R. T. Geist, S. Saporito-Irwin, N. Howells, H. Ponta, P. Herrlich and D. H. Gutmann. 1997. Interdomain binding mediates tumor growth suppression by the NF2 gene product. Oncogene 15, 2505-2509 https://doi.org/10.1038/sj.onc.1201418
  19. Trofatter, J. A, M. M. MacCollin, J. L. Rutter, J. R. Murrell, M. P. Duyao, D. M. Parry, R. Eldridge, N. Kley, A. G. Menon and K Pulaski. 1993. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 72, 791-800 https://doi.org/10.1016/0092-8674(93)90406-G
  20. Tsukita, S. and S. Yonemura. 1997. ERM (ezrin/radixin/rnoesin) family: from cytoskeleton to signal transduction. Curr. Opin. Cell Biol. 9, 70-75 https://doi.org/10.1016/S0955-0674(97)80154-8
  21. Tsukita, S., K Oishi, N. Sato, J. Sagara, A. Kawai and S. Tsukita. 1994. ERM family members as molecular linkers between the cell surface glycoprotein CD44 and actin-based cytoskeletons. J. Cell Biol. 126, 391-401 https://doi.org/10.1083/jcb.126.2.391
  22. Tsukita, S., S. Yonemura and S. Tsukita. 1997. ERM proteins: head-to-tail regulation of actin-plasma membrane interaction. Trends Biochem. Sci. 22, 53-58 https://doi.org/10.1016/S0968-0004(96)10071-2
  23. Turunen, O., M. Sainio, J. Jaaskelaninen, O. Carpen and A. Vaheri. 1998. Structure-function relationships in the ezrin family and the effect of tumor-associated point mutations in neurofibromatosis 2 protein. Biochim. Biophys. Acta. 1387, 1-16 https://doi.org/10.1016/S0167-4838(98)00103-4
  24. Turunen, O., T. Wahlstrom and A. Vaheri. 1994. Ezrin has a COOH-terminal actin-binding site that is conserved in the ezrin protein family. J. Cell Biol. 126, 1445-1453 https://doi.org/10.1083/jcb.126.6.1445
  25. Takahashi, K, T. Sasaki, A. Mammoto, K Takaishi, T. Kameyama, S. Tsukita and Y. Takai. 1997. Direct interaction of the Rho GDP dissociation inhibitor with ezrin/radixin/moesin initiates the activation of the Rho small G protein. J. Biol. Chem. 272, 23371-23375 https://doi.org/10.1074/jbc.272.37.23371
  26. Xu, G. F., P. O'Connell, D. Viskochi, R. Cawthon, M. Robertson, M. Culver, D. Dunn, J. Stevens, R. Gesteland and R. White. 1990. The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 62, 599-608 https://doi.org/10.1016/0092-8674(90)90024-9
  27. Yonemura, S., M. Hirao, Y. Doi, N. Takahashi, T. Hondo, S. Tsukita and S. Tsukita. 1998. Ezrin/radixin/rnoesin (ERM) proteins bind to a positively charged amino acid cluster in the juxta-membrane cytoplasmic domain of CD44, CD43, and ICAM-2. J. Cell Biol. 140, 885-895 https://doi.org/10.1083/jcb.140.4.885