Article abstract


Nature Cell Biology 8, 27 - 36 (2006)
Published online: 11 December 2005 | doi:10.1038/ncb1339

The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis

Fisun Hamaratoglu1,2, Maria Willecke2,3, Madhuri Kango-Singh2, Riitta Nolo2, Eric Hyun1,2, Chunyao Tao2, Hamed Jafar-Nejad4 & Georg Halder1,2,5


Merlin, the protein product of the Neurofibromatosis type-2 gene, acts as a tumour suppressor in mice and humans. Merlin is an adaptor protein with a FERM domain and it is thought to transduce a growth-regulatory signal. However, the pathway through which Merlin acts as a tumour suppressor is poorly understood. Merlin, and its function as a negative regulator of growth, is conserved in Drosophila, where it functions with Expanded, a related FERM domain protein. Here, we show that Drosophila Merlin and Expanded are components of the Hippo signalling pathway, an emerging tumour-suppressor pathway. We find that Merlin and Expanded, similar to other components of the Hippo pathway, are required for proliferation arrest and apoptosis in developing imaginal discs. Our genetic and biochemical data place Merlin and Expanded upstream of Hippo and identify a pathway through which they act as tumour-suppressor genes.

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  1. Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
  2. Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
  3. Interfakultäres Institut für Zellbiologie, Abt. Genetik der Tiere, Universität Tübingen, 72076 Tübingen, Germany.
  4. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  5. Program in Genes and Development, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

Correspondence to: Georg Halder1,2,5 e-mail: ghalder@mdanderson.org



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