Nuclear translocation of integrin cytoplasmic domain-associated protein 1 stimulates cellular proliferation.
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 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 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. Together, these results demonstrate that ICAP-1 shuttles between the nucleus and cytoplasm in a beta1 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.
Fournier
Henri-Noël
HN
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, La Tronche Cedex, France.
Dupé-Manet
Sandra
S
Bouvard
Daniel
D
Luton
Frédéric
F
Degani
Simona
S
Block
Marc R
MR
Retta
Saverio Francesco
SF
Albiges-Rizo
Corinne
C
D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D004285:Dogs; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation / Q000235:genetics; D019913:Nuclear Localization Signals / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C108257:ITGB1BP1 protein, human; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D019913:Nuclear Localization Signals