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

Roberta Ferretti, Valeria Palumbo, Augusta Di Savino, Silvia Velasco, Mauro Sbroggiò, Paolo Sportoletti, Lucia Micale, Emilia Turco, Lorenzo Silengo, Gioacchino Palumbo, Emilio Hirsch, Julie Teruya-Feldstein, Silvia Bonaccorsi, Pier Paolo Pandolfi, Maurizio Gatti, Guido Tarone, Mara Brancaccio

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)486-495
Number of pages10
JournalDevelopmental Cell
Volume18
Issue number3
Publication statusPublished - Mar 16 2010

ASJC Scopus subject areas

  • Developmental Biology

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