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

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

FERRETTI, Roberta;DI SAVINO, AUGUSTA;SBROGGIO', Mauro;TURCO, Emilia;SILENGO, Lorenzo;HIRSCH, Emilio;PANDOLFI DE RINALDIS, Pier Paolo;TARONE, Guido;BRANCACCIO, Mara
2010

Abstract

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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Ferretti R; Palumbo V; Di Savino A; Velasco S; Sbroggiò M; Sportoletti P; Micale L; Turco E; Silengo L; Palumbo G; Hirsch E; Teruya-Feldstein J; Bonaccorsi S; Pandolfi PP; Gatti M; Tarone G; Brancaccio M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/74409
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