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Vol. 16, Issue 4, 1859-1871, April 2005

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Nuclear Translocation of Integrin Cytoplasmic Domain-associated Protein 1 Stimulates Cellular Proliferation

Henri-Noël Fournier ^*, Sandra Dupé-Manet ^*, Daniel Bouvard ^*, Frédéric Luton , Simona Degani , Marc R. Block ^*, Saverio Francesco Retta , and Corinne Albiges-Rizo ^*

^* Laboratoire d'Etude de la Différenciation et de l'Adhérence Cellulaires, Unité Mixte Recherche Université Joseph Fourier/Centre National de la Recherche Scientifique 5538 Institut Albert Bonniot, Faculté de Médecine de Grenoble, Domaine de la Merci, 38706 La Tronche Cedex, France; Dynamique Moléculaire des Compartiments Cellulaires, Institut de Pharmacologie du Centre National de la Recherche Scientifique, 06560 Sophia Antipolis, France; and Department of Genetics, Biology, and Biochemistry, University of Torino, 10149 Turin, Italy

Submitted August 27, 2004; Accepted January 26, 2005
Monitoring Editor: Mark Ginsberg

Integrin cytoplasmic domain-associated protein 1 (ICAP-1) has been shown to interact specifically with the 1 integrin cytoplasmic domain and to control cell spreading on fibronectin. Interestingly, ICAP-1 also is observed in the nucleus, by immunocytochemical staining, and after biochemical cell fractionation, suggesting that it has additional roles that have yet to be determined. We show that the nucleocytoplasmic shuttling capability of ICAP-1 is dependent on a functional nuclear localization signal. In addition, overexpression of 1 integrin strongly reduced this nuclear localization, suggesting that integrin activity could modulate ICAP-1 shuttling by sequestering it in the cytoplasm. Indeed, the nuclear localization of ICAP-1 is dependent on the stage of cell spreading on fibronectin, and we also show that ICAP-1 expression stimulates cellular proliferation in a fibronectin-dependent manner. This function is dependent on its nuclear localization. Moreover, ICAP-1 is able to activate the c-myc promoter in vitro. Together, these results demonstrate that ICAP-1 shuttles between the nucleus and cytoplasm in a 1 integrin-dependent manner. It could act as a messenger that relays information from sites of integrin-dependent cell adhesion to the nucleus for controlling gene expression and cell proliferation.

Address correspondence to: Corinne Albiges-Rizo (corinne.albiges-rizo{at}ujf-grenoble.fr).

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