Interdomain binding mediates tumor growth suppression by the NF2 gene product

Lawrence (Larry) Sherman, Hua Mei Xu, Robert T. Geist, Susan Saporito-Irwin, Norma Howells, Helmut Ponta, Peter Herrlich, David H. Gutmann

Research output: Contribution to journalArticle

194 Citations (Scopus)

Abstract

The neurofibromatosis 2 (NF2) tumor suppressor gene encodes an intracellular membrane-associated protein, called merlin (or schwannomin), that belongs to the band 4.1 family of cytoskeleton-associated proteins. Inactivating NF2 mutations occur in several sporadic tumor types and have been linked to the NF2 disease, whose hallmark is the development of bilateral Schwann cell tumors (schwannomas) of the eighth cranial nerve. Two major alternatively spliced NF2 variants are expressed in normal tissues: 'NF2-17' lacking exon 16 and 'NF2-16' that contains exon 16 and encodes a merlin protein truncated at the C-terminus. We report that overexpression of NF2-17 in rat schwannoma cells inhibits their growth in vitro and in vivo, while NF2-16 fails to influence schwannoma growth. Tumor growth inhibition by merlin depends on an interdomain association occurring either in cis or in trans between the N- and C-termini. This association does not occur in the truncated NF2-16 protein nor in a mutant NF2-17 protein lacking C-terminal sequences. These data indicate that merlin has a unique mechanism of tumor suppression, inhibiting cell proliferation via self-association.

Original languageEnglish (US)
Pages (from-to)2505-2509
Number of pages5
JournalOncogene
Volume15
Issue number20
StatePublished - 1997
Externally publishedYes

Fingerprint

Neurofibromin 2
Neurofibromatosis 2
Growth
Neoplasms
Neurilemmoma
Exons
Vestibulocochlear Nerve
Intracellular Membranes
Proteins
Schwann Cells
Protein C
Tumor Suppressor Genes
Cytoskeleton
Membrane Proteins

Keywords

  • ERM proteins
  • Merlin
  • Negative growth regulator
  • Schwannoma
  • Schwannomin
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Sherman, L. L., Xu, H. M., Geist, R. T., Saporito-Irwin, S., Howells, N., Ponta, H., ... Gutmann, D. H. (1997). Interdomain binding mediates tumor growth suppression by the NF2 gene product. Oncogene, 15(20), 2505-2509.

Interdomain binding mediates tumor growth suppression by the NF2 gene product. / Sherman, Lawrence (Larry); Xu, Hua Mei; Geist, Robert T.; Saporito-Irwin, Susan; Howells, Norma; Ponta, Helmut; Herrlich, Peter; Gutmann, David H.

In: Oncogene, Vol. 15, No. 20, 1997, p. 2505-2509.

Research output: Contribution to journalArticle

Sherman, LL, Xu, HM, Geist, RT, Saporito-Irwin, S, Howells, N, Ponta, H, Herrlich, P & Gutmann, DH 1997, 'Interdomain binding mediates tumor growth suppression by the NF2 gene product', Oncogene, vol. 15, no. 20, pp. 2505-2509.
Sherman LL, Xu HM, Geist RT, Saporito-Irwin S, Howells N, Ponta H et al. Interdomain binding mediates tumor growth suppression by the NF2 gene product. Oncogene. 1997;15(20):2505-2509.
Sherman, Lawrence (Larry) ; Xu, Hua Mei ; Geist, Robert T. ; Saporito-Irwin, Susan ; Howells, Norma ; Ponta, Helmut ; Herrlich, Peter ; Gutmann, David H. / Interdomain binding mediates tumor growth suppression by the NF2 gene product. In: Oncogene. 1997 ; Vol. 15, No. 20. pp. 2505-2509.
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