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Publication : Morgana/chp-1, a ROCK inhibitor involved in centrosome duplication and tumorigenesis.

First Author  Ferretti R Year  2010
Journal  Dev Cell Volume  18
Issue  3 Pages  486-95
PubMed ID  20230755 Mgi Jnum  J:159109
Mgi Id  MGI:4441223 Doi  10.1016/j.devcel.2009.12.020
Citation  Ferretti R, et al. (2010) Morgana/chp-1, a ROCK inhibitor involved in centrosome duplication and tumorigenesis. Dev Cell 18(3):486-95
abstractText  Centrosome abnormalities lead to genomic instability and are a common feature of many cancer cells. Here we show that mutations in morgana/chp-1 result in centrosome amplification and lethality in both Drosophila and mouse, and that the fly centrosome phenotype is fully rescued by the human ortholog of morgana. In mouse cells, morgana forms a complex with Hsp90 and ROCK I and II, and directly binds ROCK II. Morgana downregulation promotes the interaction between ROCK II and nucleophosmin (NPM), leading to an increased ROCK II kinase activity, which results in centrosome amplification. Morgana(+/-) primary cells and mice display an increased susceptibility to neoplastic transformation. In addition, tumor tissue array histochemical analysis revealed that morgana is underexpressed in a large fraction of breast and lung human cancers. Thus, morgana/chp-1 appears to prevent both centrosome amplification and tumorigenesis.
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