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 / Roberta, Ferretti; Palumbo, VALERIA LUCIANA; Augusta Di, Savino; Silvia, Velasco; Mauro, Sbroggio; Paolo, Sportoletti; Lucia, Micale; Emilia, Turco; Lorenzo, Silengo; Gioacchino, Palumbo; Emilio, Hirsch; Julie Teruya, Feldstein; Bonaccorsi, Silvia; Pier Paolo, Pandolfi; Gatti, Maurizio; Guido, Tarone; Mara, Brancaccio. - In: DEVELOPMENTAL CELL. - ISSN 1534-5807. - STAMPA. - 18:3(2010), pp. 486-495. [10.1016/j.devcel.2009.12.020]
Morgana/chp-1, a ROCK Inhibitor Involved in Centrosome Duplication and Tumorigenesis
PALUMBO, VALERIA LUCIANA;BONACCORSI, Silvia;GATTI, MAURIZIO;
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
