Missense mutations in the NF2 gene result in the quantitative loss of merlin protein and minimally affect protein intrinsic function

Proceedings of the National Academy of Sciences of the United States of America

Volumn 108, Issue 12, 2011, Pages 4980-4985

  Yang, Chunzhang ^a   Asthagiri, Ashok R ^a   Iyer, Rajiv R ^a   Lu, Jie ^a   Xu, David S ^a   Ksendzovsky, Alexander ^a   Brady, Roscoe O ^a   Zhuang, Zhengping ^a   Lonser, Russell R ^a  

^a NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MERLIN; MESSENGER RNA; MUTANT PROTEIN;

ARTICLE; CONTROLLED STUDY; DEGRADATION KINETICS; GENE EXPRESSION; GENETIC TRANSFECTION; HALF LIFE TIME; HOMEOSTASIS; HUMAN; HUMAN CELL; HUMAN TISSUE; MISSENSE MUTATION; NEUROFIBROMATOSIS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TUMOR CELL; TUMOR GROWTH; TUMOR SUPPRESSOR GENE;

CELL LINE, TUMOR; CENTRAL NERVOUS SYSTEM NEOPLASMS; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE SILENCING; GENES, NEUROFIBROMATOSIS 2; HUMANS; MUTATION, MISSENSE; NEUROFIBROMATOSIS 2; NEUROFIBROMIN 2; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION;

EID: 79953217085     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1102198108     Document Type: Article

References (25)

1. Martuza RL, Eldridge R (1988) Neurofibromatosis 2 (bilateral acoustic neurofibromatosis). N Engl J Med 318:684-688.
2. Trofatter JA, et al. (1993) A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 72:791-800. (Pubitemid 23093886)
3. Lallemand D, Curto M, Saotome I, Giovannini M, McClatchey AI (2003) NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions. Genes Dev 17:1090-1100. (Pubitemid 36534984)
4. McClatchey AI, Giovannini M (2005) Membrane organization and tumorigenesis-the NF2 tumor suppressor, Merlin. Genes Dev 19:2265-2277. (Pubitemid 41396902)
5. Asthagiri AR, et al. (2009) Neurofibromatosis type 2. Lancet 373:1974-1986.
6. Asthagiri AR, Helm GA, Sheehan JP (2007) Current concepts in management of meningiomas and schwannomas. Neurol Clin 25:1209-1230. (Pubitemid 47600576)
7. Gautreau A, et al. (2002) Mutant products of the NF2 tumor suppressor gene are degraded by the ubiquitin-proteasome pathway. J Biol Chem 277:31279-31282. (Pubitemid 34968924)
8. Ragel BT, et al. (2008) A comparison of the cell lines used in meningioma research. Surg Neurol 70:295-307, discussion 307.
9. Mackay DJ, Esch F, Furthmayr H, Hall A (1997) Rho- and rac-dependent assembly of focal adhesion complexes and actin filaments in permeabilized fibroblasts: an essential role for ezrin/radixin/moesin proteins. J Cell Biol 138:927-938. (Pubitemid 27365053)
10. Jay V, Edwards V (1996) Filamentous aggregates in a meningioma. Ultrastruct Pathol 20:577-583. (Pubitemid 26414473)
11. James MF, et al. (2008) Modeling NF2 with human arachnoidal and meningioma cell culture systems: NF2 silencing reflects the benign character of tumor growth. Neurobiol Dis 29:278-292.
12. Gutmann DH, et al. (1999) Increased expression of the NF2 tumor suppressor gene product, merlin, impairs cell motility, adhesion and spreading. Hum Mol Genet 8:267-275. (Pubitemid 29054268)
13. Saydam O, et al. (2009) Downregulated microRNA-200a in meningiomas promotes tumor growth by reducing E-cadherin and activating the Wnt/beta-catenin signaling pathway. Mol Cell Biol 29:5923-5940.
14. Gupta V, Samuleson CG, Su S, Chen TC (2007) Nelfinavir potentiation of imatinib cytotoxicity in meningioma cells via survivin inhibition. Neurosurg Focus 23:E9.
15. Huang J, Chen J (2008) VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation. Oncogene 27:4056-4064. (Pubitemid 351931990)
16. Wenzel T, Baumeister W (1995) Conformational constraints in protein degradation by the 20S proteasome. Nat Struct Biol 2:199-204.
17. Lu J, et al. (2010) Decreased glucocerebrosidase activity in Gaucher disease parallels quantitative enzyme loss due to abnormal interaction with TCP1 and c-Cbl. Proc Natl Acad Sci USA 107:21665-21670.
18. McClellan AJ, Scott MD, Frydman J (2005) Folding and quality control of the VHL tumor suppressor proceed through distinct chaperone pathways. Cell 121:739-748. (Pubitemid 40797596)
19. Knudson AG, Jr (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68:820-823.
20. Knudson AG (2001) Two genetic hits (more or less) to cancer. Nat Rev Cancer 1:157-162.
21. Hitotsumatsu T, et al. (1997) Expression of neurofibromatosis 2 protein in human brain tumors: an immunohistochemical study. Acta Neuropathol 93:225-232. (Pubitemid 27104417)
22. Ahronowitz I, et al. (2007) Mutational spectrum of the NF2 gene: a meta-analysis of 12 years of research and diagnostic laboratory findings. Hum Mutat 28:1-12. (Pubitemid 46036208)
23. Nordstrom-O'Brien M, et al. Genetic analysis of von Hippel-Lindau disease. Hum Mutat 31:521-537.
24. Shimizu T, et al. (2002) Structural basis for neurofibromatosis type 2. Crystal structure of the merlin FERM domain. J Biol Chem 277-10332-10336. (Pubitemid 34968150)
25. Furuta M, et al. (2004) Protein patterns and proteins that identify subtypes of glioblastoma multiforme. Oncogene 23:6806-6814. (Pubitemid 39280012)