Letter abstract
Nature Cell Biology 5, 914 - 920 (2003)
Published online: 21 September 2003 | doi:10.1038/ncb1050
Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway
Ryan S. Udan1,2,4, Madhuri Kango-Singh2,4, Riitta Nolo2, Chunyao Tao2 & Georg Halder1,2,3
Proliferation and apoptosis must be precisely regulated to form organs with appropriate cell numbers and to avoid tumour growth1, 2. Here we show that Hippo (Hpo), the Drosophila homologue of the mammalian Ste20-like kinases3, MST1/2, promotes proper termination of cell proliferation and stimulates apoptosis during development. hpo mutant tissues are larger than normal because mutant cells continue to proliferate beyond normal tissue size and are resistant to apoptotic stimuli that usually eliminate extra cells. Hpo negatively regulates expression of Cyclin E to restrict cell proliferation, downregulates the Drosophila inhibitor of apoptosis protein DIAP1, and induces the proapoptotic gene head involution defective (hid) to promote apoptosis. The mutant phenotypes of hpo are similar to those of warts (wts), which encodes a serine/threonine kinase of the myotonic dystrophy protein kinase family4, 5, and salvador (sav), which encodes a WW domain protein that binds to Wts6, 7. We find that Sav binds to a regulatory domain of Hpo that is essential for its function, indicating that Hpo acts together with Sav and Wts in a signalling module that coordinately regulates cell proliferation and apoptosis.
- Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
- Department of Biochemistry and Molecular Biology, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
- The Genes and Development Graduate Program, The University of Texas Graduate School of Biomedical Sciences, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
- These authors contributed equally to this work.
Correspondence to: Georg Halder1,2,3 e-mail: ghalder@mdanderson.org
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