14-MERLIN' - PERSPECTIVES OPINION Merlin and ERM proteins...

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PERSPECTIVES members 8,9 .However, in mammalian tissues, the ERM proteins show nearly exclusive expression patterns, indicating that — at least in some tissues — they might perform unique functions. The ERM proteins localize similarly within cells, interact with common partners and have similar models of regulation. Merlin and ERM functions have been impli- cated in a broad range of cellular activities and cell types.Although some interesting similari- ties and differences between merlin and the ERMs have been identified, most studies have focused on either merlin or the ERMs without comparing them (BOX 2;reviewed in REF.10). So, do merlin and the ERM proteins have similar functions? Despite their close similarity to merlin, the ERM proteins are not known to function as tumour suppressors. Indeed, several studies indicate the opposite — that the ERMs have a positive function in cell transformation, cell survival, cell motility and tumour inva- sion 11–16 .Several recent studies have linked increased ezrin expression to tumour metas- tasis 14–16 .Invertebrate genomes contain both merlin and single ERM homologues, indicat- ing evolutionarily distinct functions 10 .Yet merlin and ERM proteins are co-expressed in most cell types, share binding partners and can physically interact with one another, indi- cating that they share a functional relationship. When compared, merlin and ERM proteins seem to show subcellular distributions that are generally distinct but overlapping; so, pools of merlin and ERM proteins might co-localize under certain conditions 10,17 .Defining the relationship between merlin and the ERMs is pivotal to considering their respective roles in cancer development, and several scenarios are possible. Merlin and the ERMs could per- form unique functions, they could function antagonistically or they could function Merlin is closely related to ezrin, radixin and moesin (ERMs) — membrane– cytoskeleton-associated proteins that belong to the protein 4.1 superfamily. Although merlin is the only member of the merlin/ERM subfamily that is known to function as a tumour suppressor, common subcellular localization, shared interacting partners and physical interaction between merlin and the ERMs indicate that functional overlap exists. Mouse models indicate that merlin inactivation might have an unappreciated role in human cancer aetiology. So, could the ERM proteins also have a role in cancer development? Mutations in the NF2 tumour-suppressor gene underlie neurofibromatosis type 2 ,a familial cancer syndrome that features the develop- ment of tumours of the central nervous system — particularly schwannomas and menin- giomas 1 (BOX 1) .In 1993, the NF2 tumour- suppressor gene was identified by positional cloning and loss-of-heterozygosity studies, without any previous knowledge of the molec- ular basis for the disease 2,3 .The unexpected discovery that the NF2 -encoded protein is closely related to the membrane
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14-MERLIN' - PERSPECTIVES OPINION Merlin and ERM proteins...

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