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MBC in Press, published online ahead of print February 25, 2005
Mol. Biol. Cell 10.1091/mbc.E04-08-0744

A more recent version of this article appeared on April 1, 2005 Originally published as MBC in Press, 10.1091/mbc.E04-08-0744 on February 9, 2005
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Submitted on August 27, 2004
Accepted on January 26, 2005

Nuclear Translocation of ICAP-1 Stimulates Cellular Proliferation

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

*Laboratoire d’Etude de la Différenciation et de l’Adhérence Cellulaires, UMR UJF/CNRS 5538 Institut Albert Bonniot, Faculté de Médecine de Grenoble, Domaine de la Merci, 38706 La Tronche Cedex, France; {dagger}Dynamique Moléculaire des Compartiments Cellulaires, Institut de Pharmacologie du CNRS, 06560 Sophia Antipolis, France; {ddagger}Department of Genetics, Biology and Biochemistry, University of Torino, 10149 Turin, Italy

Monitoring Editor: Mark Ginsberg

Integrin cytoplasmic domain-associated protein 1 (ICAP-1) has been shown to interact specifically with the beta1 integrin cytoplasmic domain and to control cell spreading on fibronectin. Interestingly, ICAP-1 is also 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 beta1 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. Taken together, these results demonstrate that ICAP-1 shuttles between the nucleus and cytoplasm in a beta 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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