Revisión: Mecanismos moleculares de la neurofibromatosis tipo 2
Review: The molecular mechanisms of neurofibromatosis type 2
DOI:
https://doi.org/10.54167/tch.v6i1.686Palabras clave:
neurofibromatosis tipo 2, merlina, citoesqueleto, membrana plasmáticaResumen
En este trabajo presentamos una revisión sobre hallazgos más relevantes de la neurofibromatosis tipo 2 (NF2), la cual se conoce por ser un desorden autosómico dominante caracterizado por la presencia de schwannomas vestibulares bilaterales, aunque pueden presentarse otros tumores como meningiomas y ependimomas. Esta enfermedad es causada por diversas mutaciones en el gen NF2, mismo que codifica una proteína conocida como merlina o schwannomina. Merlina está relacionada estructuralmente con la familia de proteínas ERM (Ezrina-Radixina- Moesina), encargadas de acoplar las señales provenientes de las glucoproteínas de la membrana plasmática con el citoesqueleto de actina. El gen NF2 es considerado como un supresor de tumores, y las evidencias indican que merlina funciona regulando la proliferación y el crecimiento celular. Sin embargo, los mecanismos específicos por medio de los cuales merlina cumple con su función siguen siendo un enigma. Se han identificado diversas moléculas que interactúan con merlina, lo que ha proporcionado indicios acerca de los diversos procesos celulares en los cuales esta molécula participa. Entre las proteínas que interactúan con merlina se incluyen proteínas de función estructural, receptores de membrana plasmática, proteínas citosólicas, GTPasas y adaptadores citoesqueléticos. Las mutaciones en el gen NF2 afectan la funcionalidad de merlina, lo que produce alteraciones en los mecanismos de acción de merlina dando como origen a la NF2. Son necesarios más estudios para determinar con certeza el papel de merlina en el control de la proliferación celular.
Abstract
In this work, we present a review over the most relevant information of the neurofibromatosis type 2 (NF2), which is known as an autosomal dominant disorder characterized by the presence of bilateral vestibular schwannomas. Other tumors such as meningiomas and ependymomas may be present. The disease is caused by mutations in the NF2 gene, which encodes a protein known as merlin or schwannomin. Merlin is structurally related to the ERM (Ezrina-Radixina-Moesina) family of proteins, a group of molecules responsible for linking the signals coming from the plasma membrane glycoproteins to the actin cytoskeleton. The NF2 gene is considered as a tumor suppressor gene, and the evidence indicates that merlin functions by regulating the cell growth and proliferation. However, the specific mechanisms through which merlin fulfill its functions as a tumor suppressor remains enigmatic. Several molecules that interact with merlin have been identified. This has provided clues to determine the cellular processes in which merlin participates. These molecules include structural proteins, plasma membrane receptors, cytosolic proteins, GTPases, and cytoskeletal adapters. Mutations in the NF2 gene affect the functionality of merlin, altering tha mecanisms of action of merlin, giving rise to NF2. Further studies are needed to determine the precise role of merlin on the control of cell proliferation.
Keywords: neurofibromatosis type 2, merlin, cytoskeleton, plasma membrane.
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Alberts, B. J., A. Johnson, J. Lewis, M. Raff, K. Roberts & P. Walter. 2002. Molecular Biology of the cell. 4th Edition. Garland Publishing. ISBN 0815332181, 9780815332183.
Aplin, A. E., A. Howe, S. K. Alahari & R. L. Juliano. 1998. Signal transduction and signal modulation by cell adhesion receptors: the role of integrins, cadherins, immunoglobulin-cell adhesion molecules and selectins. Pharmacological Reviews 50(2):197-263. http://pharmrev.aspetjournals.org/content/pharmrev/50/2/197.full.pdf
Bass, M. D. & M. J. Humphries. 2002. Cytoplasmic interactions of syndecan-4 orchestrate adhesion receptor and growth factor receptor signaling. Biochemical Journal 368(Pt.1):1-15. https://doi.org/10.1042/bj20021228
Bianchi, A. B., S. I. Mitsunaga, J. Q. Cheng, W. M. Klein, S. C. Jhanwar & B. Seizinger. 1995. High frequency of inactivating mutations in the neurofibromatosis type 2 gene (NF2) in primary malignant mesotheliomas. Proceedings of the National Academy of Sciences 92(24):10854-10858. https://doi.org/10.1073%2Fpnas.92.24.10854
Bianchi, A. B., T. Hara, V. Ramesh, J. Gao,A. Klein & F. Morin. 1994. Mutations in transcript isoforms of the neurofibromatosis 2 gene in multiple human tissue types. Nature Genetics 6(2):185-192. https://doi.org/10.1038/ng0294-185
Bortner, C. D. & J. A. Cidlowski. 2002. Apoptotic volume decrease and the incredible shrinking cell. Cell Death & Differentiation 9(12):1307-1310. https://doi.org/10.1038/sj.cdd.4401126
Brault, E., A. Gautreau, M. Lamarine, I. Callebaut, G. Thomas & L. Goutebroze. 2001. Normal membrane localization and actin association of the NF2 tumor suppressor protein are dependent on folding of its N-terminal domain. Journal of Cell Science 114(Pt. 10):1901-1912. https://doi.org/10.1242/jcs.114.10.1901
Bullis, B. L., X. Li, D. N. Singh, L. G. Berthiaume & L. Fliegel. 2002. Properties of the Na+/H+ exchanger protein. Detergent-resistant aggregation and membrane microdistribution. European Journal of Biochemistry 269(19):4887-4895. https://doi.org/10.1046/j.1432-1033.2002.03202.x
Carlier, M. F., P. Nioche, I. Broutin-L’Hermite, R. Boujemaa, C. Le Clainche & Egile. 2000. GRB2 links signaling to actin assembly by enhancing interaction of neural Wiskott-Aldrich syndrome protein (N-WASp) with actin-related protein (ARP2/3) complex. Journal of Biological Chemistry 275(29):21946-21952. https://doi.org/10.1074/jbc.M000687200
Chang, L. S., E. M. Akhmametyeva, Y. Wu, L. Zhu & D. B. Welling. 2002. Multiple transcription initiation sites, alternative splicing, and differential polyadenylation contribute to the complexity of human neurofibromatosis 2 transcripts. Genomics 79(1):63-76. https://doi.org/10.1006/geno.2001.6672
Chishti, A., A. Kim, S. Marfatia, M. Lutchman, M. Hanspal & H. Jindal. 1998. The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane. Trends in Biochemical Sciences 23(8):281-282. https://doi.org/10.1016/s0968-0004(98)01237-7
Cichy, J. & E. Pure. 2003. The liberation of CD44. Journal of Cell Biology 161(5):839-843. https://doi.org/10.1083/jcb.200302098
Ciechanover, A., A. Orian & A. L. Schwartz. 2000. Ubiquitin-mediated proteolysis: biological regulation via destruction. Bioessays 22(5):442-451. https://doi.org/10.1002/(sici)1521-1878(200005)22:5%3C442::aid-bies6%3E3.0.co;2-q
Clague, M. J. & S. Urbé. 2001. The interface of receptor trafficking and signalling. Journal of Cell Science 114(Pt. 17):3075-3081. https://doi.org/10.1242/jcs.114.17.3075
Counillon, L. & J. Pouyssegur. 2000. The expanding family of eucaryotic Na(+)/H(+) exchangers. Journal of Biological Chemistry 275(1):1-4. https://doi.org/10.1074/jbc.275.1.1
Denbakker, M. A., M. Tascilar, P. H. Riegman, A. C. Hekman, W. Boersma & P. J. Janssen. 1955. Neurofibromatosis type 2 protein co-localizes with elements of the cytoskeleton. The American Journal of Pathology 147(5):1339-1349. https://tinyurl.com/23bfm5v8
Desai, A. & T. J. Mitchison. 1997. Microtubule polymerization dynamics. Annual Review of Cell and Developmental Biology 13:83-117. https://doi.org/10.1146/annurev.cellbio.13.1.83
Evans, D. G., M. Sainio & M. E. Baser. 2000. Neurofibromatosis type 2. Journal of Medical Genetics 37(12):897-904. https://doi.org/10.1136%2Fjmg.37.12.897
Evans, D. G., S. M. Huson, D. Donnai, W. Neary, V. Blair & V. Newton. 1992. A genetic study of type 2 neurofibromatosis in the United Kingdom. II. Guidelines for genetic counselling. Journal of Medical Genetics 29(12):847-852. https://doi.org/10.1136%2Fjmg.29.12.847
Evans, J., S. Jeun, J. Lee, J. Harwalkar, Y. Shoshan, J. Cowell & M. Golubic. 2001. Molecular alterations in the neurofibromatosis type 2 gene and its protein rarely occurring in meningothelial meningiomas. Journal of Neurosurgery 94(1):111–117. https://doi.org/10.3171/jns.2001.94.1.0111
Evans, D. G. 2009. Neurofibromatosis type 2 (NF2): Aclinical and molecular review. Orphanet Journal of Rare Diseases 19:4-16. https://doi.org/10.1186/1750-1172-4-16
Evans, D. G. R., S. K. Lloyd & R. T. Ramsden. 2011. Neurofibromatosis type 2. Advances in Oto-rhino-laryngology 70:91-98. https://doi.org/10.1159/000322482
Fernandez-Valle, C., Y. Tang, J. Ricard, A. Rodenas-Ruano, A.Taylor & E. Hackler. 2002. Paxillin binds schwannomin and regulates its density-dependent localization and effect on cell morphology. Nature Genetics 31(4):354-362. https://doi.org/10.1038/ng930
Fialka, I., P. Steinlein, H. Ahorn, G. Böck, P. D. Burbelo, M. Haberfellner, F. Lottspeich, K. Paiha, C. Pasquali & L.A. Huber. 1999. Identification of syntenin as a protein of the apical early endocytic compartment in Madin-Darby canine kidney cells. Journal of Biological Chemistry 274(37):26233-26239. https://doi.org/10.1074/jbc.274.37.26233
Flaiz, C., T. Utermark, D. B. Parkinson, A. Poetsch & C. O. Hanemann. 2008. Impaired intercellular adhesion and immature adherens junctions in merlin-deficient human primary schwannoma cells. Glia 56(5):506-515. https://doi.org/10.1002/glia.20629
Friedman, J. M., D. H. Gutmann, M. MacCollin & M. Riccardi. 1999. Neurofibromatosis: Phenotype, Natural History and Pathogenesis. 3rd. Edition. Johns Hopkins University Press. ISBN 080186285X, 9780801862854.
Gary, R. & A. Bretscher. 1995. Ezrin self-association involves binding of an N-terminal domain to a normally masked C-terminal domain that includes the F-actin binding site. Molecular Biology of the Cell 6(8):1061-1075. https://doi.org/10.1091%2Fmbc.6.8.1061
Gautreau, A., J. Manent, B. Fievet, D. Louvard, M. Giovannini & M. Arpin. 2002. Mutant products of the NF2 tumor suppressor gene are degraded by the ubiquitin-proteasome pathway. Journal of Biological Chemistry 277(35):31279-31282. https://doi.org/10.1074/jbc.c200125200
Gonzalez, C., L. Xu, D. Pinney, R. Beauchamp, W. Hobbs & J. Gusella. 1996. The merlin tumor suppressor localizes preferentially in membrane ruffles. Oncogene 13(6):1239-1247.
Gonzalez-Agosti, C., T. Wiederhold, M. E. Herndon, J. Gusella & V. Ramesh. 1999. Interdomain interaction of merlin isoforms and its influence on intermolecular binding to NHE- RF. Journal of Biological Chemistry 274(48):34438-34442. https://doi.org/10.1074/jbc.274.48.34438
Goutebroze, L., E. Brault, C. Muchardt, J. Camonis & G. Thomas. 2000. Cloning and characterization of SCHIP-1, a novel protein interacting specifically with spliced isoforms and naturally occurring mutant NF2 proteins. Molecular & Cellular Biology 20(5): 1699-1712. https://doi.org/10.1128%2Fmcb.20.5.1699-1712.2000
Grönholm, M., M. Sainio, F. Zhao, L. Heiska, A. Vaheri & O. Carpen. 1999. Homotypic and heterotypic interaction of the neurofibromatosis 2 tumor suppressor protein merlin and the ERM protein Ezrin. Journal of Cell Science 112(Pt 6):895-904. https://doi.org/10.1242/jcs.112.6.895
Gutmann, D. H., C.A. Haipek & K. H. Lu. 1999. Neurofibromatosis tumor suppressor protein, merlin, forms two functionally important intramolecular associations. Journal of Neuroscience Research 58(5):706-716. http://dx.doi.org/10.1002/(SICI)1097-4547(19991201)58:53.3.CO;2-Q
Gutmann, D. H., C. A. Haipek, S. P. Burke, C. X. Sun, D. R. Scoles & S. M. Pulst. 2001. The NF2 interactor, hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), associates with merlin in the «open» conformation and suppresses cell growth and motility. Human Molecular Genetics 10(8):825-834. https://doi.org/10.1093/hmg/10.8.825
Gutmann, D. H., M. Giordano, A. Fishback & A. Guha. 1997. Loss of merlin expression in sporadic meningiomas, ependymomas and schwannomas. Neurology 49(1):267-270. https://doi.org/10.1212/wnl.49.1.267
Hirao, M., N. Sato, T. Kondo, S. Yonemura, M. Monden & T. Sasaki. 1996. Regulation mechanism of ERM (ezrin/radixin/moesin) protein/plasma membrane association: possible involvement of phosphatidylinositol turnover and Rho-dependent signaling pathway. Journal of Cell Biology 135(1):37-51. https://doi.org/10.1083/jcb.135.1.37
Hirsch, N. P., A. Murphy & J. J. Radcliffe. 2001. Neurofibromatosis: clinical presentations and anaesthetic implications. British Journal of Anaesthesia 86(4):555-564. https://doi.org/10.1093/bja/86.4.555
Huang, Y. & K. K. Wang. 2001. The calpain family and human disease. Trends Mol. Med. 7(8):355-362. https://doi.org/10.1016/s1471-4914(01)02049-4
Hunter, T. 1997. Oncoprotein networks. Cell 88(3):333-346. https://doi.org/10.1016/s0092-8674(00)81872-3
James, M. F., N. Manchanda, C. Gonzalez-Agosti, J. H. Hartwig & V. Ramesh. 2001. The neurofibromatosis 2 protein product merlin selectively binds F-actin but not G-actin, and stabilizes the filaments through a lateral association. Biochemical Journal 356(Pt. 2):377-386. https://doi.org/10.1042%2F0264-6021%3A3560377
Jannatipour, M., P. Dion, S. Khan, H. Jindal, X. Fan & J. C. 2001. Laganiere. Schwannomin isoform-1 interacts with syntenin via PDZ domains. Journal of Biological Chemistry 276(35):33093-33100. https://doi.org/10.1074/jbc.M105792200
Johnson, K. C., J. L. Kissil, J. L. Fry & T. Jacks. 2002. Cellular transformation by a FERM domain mutant of the NF2 tumor suppressor gene. Oncogene 21(39):5990-5997. https://doi.org/10.1038/sj.onc.1205693
Jung, J. R., H. Kim, S. S. Jeun, J. Y. Lee, E. J. Koh & C. Ji. 2005. The phosphorylation status of merlin is important for regulating the Ras-ERK pathway. Molecules and Cells 20(2):196-200. https://koreascience.kr/article/JAKO200510103491129.page?&lang=ko
Kaempchen, K., K. Mielke, T. Utermark, S. Langmesser & C. O. Hanemann. 2003. Upregulation of the Rac1/JNK signaling pathway in primary human schwannoma cells. Hum. Mol. Genet. 12(11):1211-1221. https://doi.org/10.1093/hmg/ddg146
Kim, H., J.Y. Lim, Y. H. Kim, H. Kim, S. H. Park, S. H. & K. H. Lee. 2002. Inhibition of ras-mediated activator protein 1 activity and cell growth by merlin. Molecules and Cells 14(1):108-114. https://www.molcells.org/journal/download_pdf.php?spage=108&volume=14&number=1
Kimura, Y., H. Koga, N.Araki, N. Mugita, N. Fujita & H. Takeshima. 1998. The involvement of calpain-dependent proteolysis of the tumor suppressor NF2 (merlin) in schwannomas and meningiomas. Nature Medicine 4(8):915-922. https://doi.org/10.1038/nm0898-915
Kimura, Y., H. Saya & M. Nakao. 2000. Calpain-dependent proteolysis of NF2 protein: involvement in schwannomas and meningiomas. Neuropathology 20(3):153-160. https://doi.org/10.1046/j.1440-1789.2000.00326.x
Kissil, J. L., K. C. Jonson, M. S. Eckman & T. Jacks. 2002. Merlin phosphorylation by p21-activated kinase 2 and effects of phosphorylation on merlin localization. Journal of Biological Chemistry 277(12):10394-10399. https://doi.org/10.1074/jbc.m200083200
Knudson, A. G. 1971. Mutation and cancer: statistical study of retinoblastoma. Proceedings of the National Academy of Sciences 68(4):820-823. https://doi.org/10.1073/pnas.68.4.820
Koga, H, N. Araki, H. Takeshima, T. Nishi, T. Hirota, Y. Kimura, M. Nakao & H. Saya. 1998. Impairment of cell adhesion by expression of the mutant neurofibromatosis type 2(NF2) genes which lack exons in the ERM-homology domain. Oncogene 17(7):801-810. https://doi.org/10.1038/sj.onc.1202010
Korf, B. 2004. The phakomatoses. Neuroimaging Clinics of North America 14(2):139-148. https://doi.org/10.1016/j.nic.2004.03.008
Korf, B. R. 2005. The phakomatoses. Clinics in Dermatology 23(1):78-84. https://doi.org/10.1016/j.clindermatol.2004.09.007
Krasnoselsky, A., M. J. Massay, M. C. DeFrances, G.Michalopoulos, R. Zarnegar & N. Ratner. 1994. Hepatocyte growth factor is a mitogen for Schwann cells and is present in neurofibromas. Journal of Neuroscience 14(12):7284-7290. https://doi.org/10.1523/jneurosci.14-12-07284.1994
Lajenusse, D. R., B. M. McCartey & R. G. Fehon. 1998. Structural analysis of Drosophyla merlin reveals functional domains important for growth control and subcellular localization. Journal of Cell Biology 141(7):1589-1599. https://doi.org/10.1083/jcb.141.7.1589
Lallemand, D., M. Curto, I. Saotome, M. Giovannini & A. I. McClatchey. 2003. NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions. Genes & Development 17(9):1090-1100. https://doi.org/10.1101/gad.1054603
Lasota, J., J. F. Fetsch, A. Wozniak, B. Wasag, R. Sciot & M. Miettinen. 2001. The neurofibromatosis type 2 gene is mutated in perineurial cell tumors: a molecular genetic study of eight cases. The American Journal of Pathology 158(4):1223-1229. https://doi.org/10.1016/s0002-9440(10)64072-2
Laulajainen, M., T. Muranen, O. Carpén & M. Grönholm. 2008. Protein kinase A-mediated phosphorylation of the NF2 tumor suppressor protein merlin at serine 10 affects the actin cytoskeleton. Oncogene 27(23):3233-3243. https://doi.org/10.1038/sj.onc.1210988
Laulajainen, M., M. Melikova, T. Muranen, O. Carpén & M. Grönholm. 2012. Distinct overlapping sequences at the carboxy-terminus of merlin regulate its tumor suppressor and morphogenic activity. Journal of Cellular and Molecular Medicine 16(9):2161-2175. https://doi.org/10.1111%2Fj.1582-4934.2012.01525.x
Lee, I. K., K. S. Kim, H. Kim, J. Y. Lee, C. H. Ryu & H. J. Chun. 2004. MAP, a protein interacting with a tumor suppressor, merlin, through the run domain. Biochemical and Biophysical Research Communications 325(3):774-783. https://doi.org/10.1016/j.bbrc.2004.10.095
Lim, J. Y., H. Kim, Y. H. Kim, S. W. Kim, P. W. Huh & K. H. Lee. 2003. Merlin suppresses the SRE-dependent transcription by inhibiting the activation of Ras-ERK pathway. Biochemical and Biophysical Research Communications 302(2):238-245. https://doi.org/10.1016/s0006-291x(03)00124-4
MacDougall, N., Y. Lad, G. S. Wilkie, H. Francis-Lang, W. Sullivan & I. Davis. 2001. Merlin, the Drosophila homologue of neurofibromatosis-2, is specifically required in posterior follicle cells for axis formation in the oocyte. Development 128(5): 665-673. https://doi.org/10.1242/dev.128.5.665
Magendantz, M., M. D. Henry, A. Lander & F. Solomon. 1995. Interdomain interactions of radixin in vitro. Journal of Biological Chemistry 270(43):25324-25327. https://doi.org/10.1074/jbc.270.43.25324
Manchanda, N., A. Lyubimova, H. Y. Ho, M. F. James, J. F. Gusella, N. Ramesh, S. B. Snapper & V. Ramesh. 2005. The NF2 tumor suppressor Merlin and the ERM proteins interact with N-WASP and regulate its actin polymerization function. Jouirnal of Biological Chemistry 280(13):12517-12522. https://doi.org/10.1074/jbc.c400583200
McCartney, B. M., R. M. Kulikauskas, D. R. LaJeunese & R. G. Fehon. 2000. The NF-2 homologue, Merlin, and the tumor suppressor expanded function together in Drosophila to regulate cell proliferation and differentiation. Development 127(6):1315-1324. https://doi.org/10.1242/dev.127.6.1315
McClatchey, A. I. & M. Giovannini. 2005. Membrane organization and tumorigenesis—the NF2 tumor suppressor, Merlin. Genes & Development 19(19):2265-2277. https://doi.org/10.1101/gad.1335605
McClatchey, A., I. Saotome, V. Ramesg, J. Gusella & T. Jacks. 1997. The Nf2 tumor suppressor gene product is essential for extraembrionic development immediately prior to gastrulation. Genes & Development 11(10):1253-1265. https://doi.org/10.1101/gad.11.10.1253
Miki, H., T. Sasaki, Y. Takai & T. Takenawa. 1998. Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP. Nature 391(6662):93-96. https://doi.org/10.1038/34208
Morrison, H., L. S. Sherman, J. Legg, F. Banine, C. Isacke & C. A. Haipek. 2001. The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44. Genes & Development 15(8):968-980. https://doi.org/10.1101/gad.189601
Morrison, H., T. Sperka, J. Manent, M. Giovannini, H. Ponta, and P. Herrlich. 2007. Merlin/neurofibromatosis type 2 suppresses growth by inhibiting the activation of Ras and Rac. Cancer Research 67(2):520-527. https://doi.org/10.1158/0008-5472.can-06-1608
Muranen, T., M. Grönholm, A. Lampin, D. Lallemand, F. Zhao, M. Giovannini & O. Carpén. 2007. The tumor suppressor merlin interacts with microtubules and modulates Schwann cell microtubule cytoskeleton. Human Molecular Genetics 16(14):1742-1751. https://doi.org/10.1093/hmg/ddm122
Muranen, T., M. Grönholm, G. H. Renkema, and Carpén O. 2005. Cell cycle-dependent nucleocytoplasmic shuttling of the neurofibromatosis 2 tumour suppressor merlin. Oncogene 24(7):1150-1158. https://doi.org/10.1038/sj.onc.1208283
Murthy, A, C. Gonzalez-Agosti, E. Cordero, D. Pinney, C. Candia & F. Solomon. 1998. NHE-RF, a regulatory cofactor for Na(+)- H+ exchange, is a common interactor for merlin and ERM (MERM) proteins. Journal of Biological Chemistry 273(3):1273-1276. https://doi.org/10.1074/jbc.273.3.1273
Obremski, V. J., A. M. Hall & C. Fernandez-Valle. 1998. Merlin, the neurofibromatosis type 2 gene product, and beta 1 integrin associate in isolated and differentiating Schwann cells. Journal of Neurobiology 37(4):487-501.
Okada, T., M. Lopez-Lago & F. G. Giancotti. 2005. Merlin/NF-2 mediates contact inhibition of growth by suppressing recruitment of Rac to the plasma membrane. Journal of Cell Biology 171(2):361-371. https://doi.org/10.1083/jcb.200503165
Paduch, M., F. Jeleń & J. Otlewski. 2001. Structure of small G proteins and their regulators. Acta Biochimica Polonica 48(4):829-850. https://doi.org/10.18388/abp.2001_3850
Parry, D. M., M. M. McCollin, M. I. Kaiser-Kupfer, K. Pulaski, H. S. Nicholson, M. Bolesta, R. Eldridge, & J. F. Gusella. 1996. Germ-line mutations in the neurofibromatosis 2 gene: correlations with disease severity and retinal abnormalities. The American Journal of Human Genetics 59(3):529-539.
Pearson, M. A., D. Reczek, A. Bretscher & P. A. Karplus. 2000. Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain. Cell 101(3):259-270. https://doi.org/10.1016/S0092-8674(00)80836-3
Pelton, P. L., L. Sherman, T. Rizvi, M. Marchionni, P. Wood & R. Friedman. 1998. Ruffling membrane, stress fiber, cell spreading and proliferation abnormalities in human schwannoma cells. Oncogene 17(17):195-2209. https://doi.org/10.1038/sj.onc.1202141
Pineau, P., A. Marchio, S. Nagamori, S. Seki, P. Tiollais & A. Dejean. 2003. Homozygous deletion scanning in hepatobiliary tumor cell lines reveals alternative pathways for liver carcinogenesis. Hepatology 37(4):852-861. https://doi.org/10.1053/jhep.2003.50138
Pöyhönen, M. 1999. Epidemiological, clinical and genetic aspects of neurofibromatosis in northern Finland. Oulu University Library.
Raiborg, C. & H. Stenmark. 2002. Hrs and endocytic sorting of ubiquitinated membrane proteins. Cell Structure and Function 27(6):403-408. https://doi.org/10.1247/csf.27.403
Ramesh, V. 2004. Merlin and the ERM proteins in schwan cells, neurons and growth cones. Nature Reviews Neuroscience 5(6):462-470. https://doi.org/10.1038/nrn1407
Reed, N. & D. Gutmann. 2001. Tumorigenesis in neurofibromatosis: new insights and potential therapies. Trends in Molecular Medicine 7(4):157-162. https://doi.org/10.1016/S1471-4914(01)01955-4
Rong, R., E. I. Surace, C. A. Haipek, D. H. Gutmann & K. Ye. 2004. Serine 518 phosphorylation modulates merlin intramolecular association and binding to critical effectors important for NF2 growth suppression. Oncogene 23(52):8447- 8454. https://doi.org/10.1038/sj.onc.1207794
Rong, R., X. Tang, D. H. Gutmann & K. Ye. 2004. Neurofibromatosis 2 (NF2) tumor supresor merlin inhibits phosphatidylinositol 3-kinase through binding to PIKE-L. Proceedings of the National Academy of Sciences 101(52):18200-18205. https://doi.org/10.1073/pnas.0405971102
Rouleasu, G.A., P. Merel, M. Lutchman, M. Sanson, J. Zucman, C. Marineau, K. Hoang-Xuan, S. Demczuk, C. Desmaze, B. Plougastel, S. M. Pulst, G. Lenoir, E. Bijlsma, R. Fashold, J. Dumanski, P. de Jong, D. Parry, R. Eldrige, A. Aurias, O. Delattre & G. Thomas. 1993. Alteration in a new gene encoding a putative membrane organizing protein causes Neurofibromatosis type 2. Nature 363(6429):515-521. https://doi.org/10.1038/363515a0
Ruttledge, M. H., A. A.Andermann, C. M. Phelam, J. O. Claudio, F. Y. Han N. Chretien, S. Rangaratnam, M. MacCollin, P. Short, D. Parry, V. Michels, V. M. Riccardi, R. Weksberg, K. Kitamura, J. M. Bradburn, B. D. Hall, P. Propping & G. A. Rouleau. 1996. Type of mutation in the neurofibromatosis type 2 gene (NF2) frequently determines severity of disease. The American Journal of Human Genetics 59(2):331-342.
Sainio, M. 2000. Neurofibromatosis 2: Genetic analysis of mild disease, and biology of the gene product, Merlin. Department of Neurology and Department of Pathology. Haarman Institute. University of Helsinki. ISBN 951459018X. https://helda.helsinki.fi/bitstream/handle/10138/20543/neurofib.pdf?sequence=2&isAllowed=y
Sainio, M., F. Zhao, L. Heiska, O. Turunen, M. den Bakker & E. Zwarthoff. 1997. Neurofibromatosis 2 tumor suppressor protein colocalizes with ezrin and CD44 and associates with actin-containing cytoskeleton. Journal of Cell Science 110(Pt 18):2249-2260. https://doi.org/10.1242/jcs.110.18.2249
Schmuker, B., Y. Tang & M. Kressel. 1999. Novel alternatively spliced isoforms of the neurofibromatosis type 2 tumor suppressor are targeted to the nucleus and cytoplasmic granules. Human Molecular Genetics 8(8):1561-1570. https://doi.org/10.1093/hmg/8.8.1561
Scoles, D. R. 2008. The merlin interacting proteins reveal multiple targets for NF2 therapy. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer 1785(1):32-54. https://doi.org/10.1016/j.bbcan.2007.10.001
Scoles, D. R., D. P. Huynh, M. S. Chen, S. P. Burke, D. H. Gutmann, & S. M. Pulst. 1998. Neurofibromatosis 2 tumor supresor schwannomin interacts with BII-spectrin. Nature Genetics 18(4):354-359. https://doi.org/10.1038/ng0498-354
Scoles, D. R., D. P. Huynh, M. S. Chen, S. P. Burke, D. H. Gutmann & S. M. Pulst. 2000. The neurofibromatosis 2 tumor suppressor protein interacts with hepatocyte growth factor-regulated tyrosine kinase substrate. Human Molecular Genetics 9(11):1567-1574. https://doi.org/10.1093/hmg/9.11.1567
Scoles, D. R., V. D. Nguyen, Y. Qin, C. X. Sun, H. Morrison & D. H. Gutmann. 2002. Neurofibromatosis 2 (NF2) tumor suppressor schwannomin and its interacting protein HRS regulate STAT signaling. Human Molecular Genetics 11(25):3179-3189. https://doi.org/10.1093/hmg/11.25.3179
Shaw, R. J., A. I. McClatchey & T. Jacks. 1998. Regulation of the neurofibromatosis type 2 tumor suppressor protein, merlin, by adhesion and growth arrest stimuli. Journal of Biological Chemistry 273(13):7757- 7764. https://doi.org/10.1074/jbc.273.13.7757
Shaw, R. J., J. G. Paez, M. Curto, A. Yaktine, W. M. Pruitt & I. Saotome. 2001. The Nf2 tumor suppressor, merlin, functions in Rac-dependent signaling. Developmental Cell 1(1):63-72. https://doi.org/10.1016/s1534-5807(01)00009-0
Sheik, H. A., M. Tometsko, L. Niehouse, D. Aldeeb, P. Swalsky & S. Finkelstein. 2004. Molecular genotyping of medullary thyroid carcinoma can predict tumor recurrence. The American Journal of Surgical Pathology 28(1):101-106. https://doi.org/10.1097/00000478-200401000-00012
Sherr, C. J. 1996. Cancer cell cycles. Science 274(5293):1672-1677.
Shimizu, T., A. Seto, N. Maita, K. Hamada, S. Tsukita & T. Hakoshima. 2002. Structural Basis for Neurofibromatosis type 2. Crystal structure of the Merlin FERM domain. Journal of Biological Chemistry 277(12):10332-10336. https://doi.org/10.1074/jbc.m109979200
Stamenkovic, I. & Q.Yu. 2010. Merlin, a «Magic» Linker Between the Extracellular Cues and Intracellular Signaling Pathways that Regulate Cell Motility, Proliferation, and Survival. Current Protein & Peptide Science 11(6):471-484. https://doi.org/10.2174/138920310791824011
Stemmer-Rachamimov, A. O., L. Xu, C. Gonzalez-Agosti, J. A. Burwick, D. Pinney & R. Beauchamp. 1997. Universal absence of merlin, but not other ERM family members, in schwannomas. The American Journal of Pathology 151(6):1649-1654. https://europepmc.org/article/med/9403715
Stern, R. 2003. Devising a pathway for hyaluronan catabolism: are we there yet? Glycobiology 13(12):105R-115R. https://doi.org/10.1093/glycob/cwg112
Stickney, J. T., W. C. Bacon, M. Rojas, N. Ratner & W. Ip. 2004. Activation of the tumor suppressor merlin modulates its interaction with lipid rafts. Cancer Research 64(8):2717-2724 https://doi.org/10.1158/0008-5472.can-03-3798
Stokowski, R. P. & R. D. Cox. 2000. Functional analysis of the neurofibromatosis type 2 protein by means of disease-causing point mutations. The American Journal of Human Genetics 66(3):873-891. https://doi.org/10.1086/302812
Sun, C. X., C. Haipek, D. R. Scoles, S. M. Pulst, M. Giovannini & M. Komada. 2002b. Functional analysis of the relationship between the neurofibromatosis 2 tumor suppressor and its binding partner, hepatocyte growth factor-regulated tyrosine kinase substrate. Human Molecular Genetics 11(25):3167-3178. https://doi.org/10.1093/hmg/11.25.3167
Sun, C. X., V. A. Robb & D. H.Gutmann. 2002. Protein 4.1 tumor suppressors: getting a FERM grip on growth regulation. Journal of Cell Science 115(Pt. 21):3991-4000. https://doi.org/10.1242/jcs.00094
Surace, E. I., C. A. Haipek & D. H. Gutmann. 2004. Effect of merlin phosphorylation on neurofibromatosis 2 (NF2) gene function. Oncogene 23(2):580-587. https://doi.org/10.1038/sj.onc.1207142
Suzuki, K., S. Hata, Y. Kawabata & H. Sorimachi. 2004. Structure, activation, and biology of calpain. Diabetes 53(Suppl 1):S12-S18. https://doi.org/10.2337/diabetes.53.2007.s12
Takai, Y., T. Sasaki & T. Matozaki. 2001. Small GTP-binding proteins. Physiological Reviews 81(1):153-208. https://doi.org/10.1152/physrev.2001.81.1.153
Tang, X., S. W. Jang, X. Wang, Z. Liu, S. M. Bahr, S. Y. Sun, D. Brat, D. H. Gutmann & K. Ye. 2007. Akt phosphorylation regulates the tumour-suppressor merlin through ubiquitination and degradation. Nature Cell Biology 9(10):1199-1207. https://doi.org/10.1038/ncb1641
Tikoo, A., M. Varga, V. Ramesh, J. Gusella & H. Maruta. 1994. An anti-Ras function of neurofibromatosis type 2 gene product (NF2/Merlin). Journal of Biological Chemistry 269(38):23387-23390. http://dx.doi.org/10.1016/S0021-9258(17)31525-9
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, K. Pulaski, V. H. Haase, C. M. Ambrose, D. Munroe, C. Bove, J. L. Haines, R. L. Martuza, M. E. MacDonald, B. R. Seizinger, M. P. Short, A.J. Buckler & J.F. Gusella.. 1993. A novel moesin-, ezrin-, radixin- like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 72(5):791-800. https://doi.org/10.1016/0092-8674(93)90501-g
Tsukita, S., K. Oishi, N. Sato, J. Sagara, A. Kawai & S. Tsukita. 1994. ERM family members as molecular linkers between the cell surface glycoprotein CD44 and actin-based cytoskeleton. Journal of Cell Biology 126(2):391-401. https://doi.org/10.1083/jcb.126.2.391
Turner, C. E. 2000. Paxillin interactions. Journal of Cell Science 113(Pt 23):4139-4140. https://doi.org/10.1242/jcs.113.23.4139
Ueki, K., C. Wen-Bin, Y. Narita, A. Asai & T. Kirino. 1999. Tight association of loss of merlin expression with loss of heterozygosity at chromosome 22q in sporadic meningiomas. Cancer Research 59(23):5995-5998. https://aacrjournals.org/cancerres/article/59/23/5995/505676/Tight-Association-of-Loss-of-Merlin-Expression
Welling, D. B. 1998. Clinical manifestations of mutations in the neurofibromatosis type 2 gene in vestibular schwannomas (acoustic neuromas). Laryngoscope 108(2):178-189. https://doi.org/10.1097/00005537-199802000-00005
Welling, D. B., E. M. Akhmametyeva, R. L. Daniels, J. M. Lasak, L. Zhu, B. A. Miles-Markley & L. S. Chang. 2000. Analysis of the human neurofibromatosis type 2 gene promoter and its expression. Otolaryngology-Head and Neck Surgery 123(4):413-418. https://doi.org/10.1067/mhn.2000.107683
Wennerberg, K. & C. J. Der. 2004. Rho-family GTPases: it’s not only Rac and Rho (and I like it). Journal of Cell Science 117(Pt 8):1301-1312. https://doi.org/10.1242/jcs.01118
Wiederhold, T., M. F. Lee, M. James, R. Neujahr, N. Smith, A. Murthy, J. Hartwig, J. F. Gusella & V. Ramesh. 2004. Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2. Oncogene 23(54): 8815-8825. https://doi.org/10.1038/sj.onc.1208110
Wolff, R. K., K. A. Frazer, R. K. Jackler, M. J. Lanser, L. H. Pitts & D.R. Cox. 1992. Analysis of chromosome 22 deletions in neurofibromatosis related tumors. American Journal of Human Genetics 51(3):478- 485.
Wu, K. L., S. Khan, S. Lakhe-Reddy, G. Jarad, A. Mukherjee & C.A. Obejero-Paz. 2004. The NHE1 Na /H exchanger recruits ezrin/radixin/moesin proteins to regulate Akt-dependent cell survival. Journal of Biological Chemistry 279(25):26280-26286. https://doi.org/10.1074/jbc.m400814200
Xiao, G. H., A. Beeper, J. Chernoff & J. R. Testa. 2002. p21- activated kinase links Rac/Cdc42 signaling to merlin. Journal of Biological Chemistry 277(2):883-886. p21- activated kinase links Rac/Cdc42 signaling to merlin.
Xiao, G. H., J. Chernoff & J. R. Testa. 2003. NF2: The wizardry of Merlin. Genes Chromosomes Cancer 38(4):389-399. https://doi.org/10.1002/gcc.10282
Xiao, G. H., R. Gallagher, J. Shetler, K. Suele, D.A.Altomare & R. G. Pestell. 2005. The NF2 tumor suppressor gene product, merlin, inhibits cell proliferation and cell cycle progression by repressing cyclin D1 expression. Molecular & Cellular Biology 25(6):2384-2394. https://doi.org/10.1128%2FMCB.25.6.2384-2394.2005
Xu, L. & D. H. Gutmann. 1998. Merlin differentially associates with microtubule and actin cytoskeleton. Journal of Neuroscience Research 51(3):403-415. https://doi.org/10.1002/(sici)1097-4547(19980201)51:3%3C403::aid-jnr13%3E3.0.co;2-7
Yamasaki, L. & M. Pagano. 2004. Cell cycle, proteolysis and cancer. Current Opinion in Cell Biology 16(6):623-628. https://doi.org/10.1016/j.ceb.2004.08.005
Ye, K., B. Aghdasi, H. R. Luo, J. L. Moriarity, F. Y. Wu & J. J. Hong. 2002. Phospholipase C gamma 1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE. Nature 415(6871):541–544. https://doi.org/10.1038/415541a
Ye, K. 2007. Phosphorylation of merlin regulates its stability and tumor suppressive activity. Cell Adhesion & Migration 1(4):196-198. https://doi.org/10.4161%2Fcam.1.4.5192
Zucman-Rossi, J., P. Legoix, H. Der Sarkissian, G. Cheret, F. Sor, A. Bernardi, L. Cazes, S. Giraud, E. Ollagnon, G. Lenoir & G. Thomas. 1998. NF2 gene in neurofibromatosis type 2 patients. Human Molecular Genetics 7(13):2095-2101. https://doi.org/10.1093/hmg/7.13.2095
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