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PMID:16341207

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Citation

Hamaratoglu, F, Willecke, M, Kango-Singh, M, Nolo, R, Hyun, E, Tao, C, Jafar-Nejad, H and Halder, G (2006) The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis. Nat. Cell Biol. 8:27-36

Abstract

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.

Links

PubMed Online version:10.1038/ncb1339

Keywords

Animals; Apoptosis; Cell Cycle; Cell Proliferation; Cyclin E/metabolism; Drosophila/metabolism; Drosophila Proteins/chemistry; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila Proteins/physiology; Genes, Neurofibromatosis 2; Intracellular Signaling Peptides and Proteins; Male; Membrane Proteins/genetics; Membrane Proteins/physiology; Mutation; Nuclear Proteins/metabolism; Protein Kinases/metabolism; Protein-Serine-Threonine Kinases/chemistry; Protein-Serine-Threonine Kinases/metabolism; Signal Transduction; Trans-Activators/metabolism; Transcriptional Activation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:EXPA

involved_in

GO:0043065: positive regulation of apoptotic process

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0086384

P

Seeded From UniProt

complete

DROME:EXPA

involved_in

GO:0045571: negative regulation of imaginal disc growth

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0011739

P

Seeded From UniProt

complete

DROME:EXPA

involved_in

GO:0046621: negative regulation of organ growth

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0086384

P

Seeded From UniProt

complete

DROME:EXPA

involved_in

GO:0008285: negative regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0086384

P

Seeded From UniProt

complete

DROME:EXPA

involved_in

GO:0035332: positive regulation of hippo signaling

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0261456

P

Seeded From UniProt

complete

DROME:MERH

involved_in

GO:0043065: positive regulation of apoptotic process

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0004583

P

Seeded From UniProt

complete

DROME:MERH

involved_in

GO:0046621: negative regulation of organ growth

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0004583

P

Seeded From UniProt

complete

DROME:MERH

involved_in

GO:0008285: negative regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0004583

P

Seeded From UniProt

complete

DROME:MERH

involved_in

GO:0035332: positive regulation of hippo signaling

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0004583,FB:FBgn0261456

P

Seeded From UniProt

complete

DROME:YAP1

enables

GO:0003713: transcription coactivator activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:YAP1

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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