Integrin-linked kinase regulates the nuclear entry of the c-Jun coactivator alpha-NAC and its coactivation potency.
Overexpression of the integrin-linked kinase (ILK) was shown to increase c-Jun-dependent transcription. We now show that this effect of ILK involves the c-Jun transcriptional coactivator, nascent polypeptide-associated complex and coactivator alpha (alpha-NAC). ILK phosphorylated alpha-NAC on residue Ser-43 upon adhesion of cells to fibronectin. Co-expression of constitutively active ILK with alpha-NAC led to the nuclear accumulation of the coactivator. Conversely, alpha-NAC remained in the cytoplasm of cells transfected with a dominant-negative ILK mutant, and a mutated alpha-NAC at phosphoacceptor position Ser-43 (S43A) also localized outside of the nucleus. The S43A alpha-NAC mutant could not potentiate the effect of ILK on c-Jun-dependent transcription. We conclude that ILK-dependent phosphorylation of alpha-NAC induced the nuclear accumulation of the coactivator and that phosphorylation of alpha-NAC by ILK is required for the potentiation of c-Jun-mediated responses by the kinase. The results represent one of the rare examples of a transcriptional coactivator shuttling between the cytosol and the nucleus.
Quélo
Isabelle
I
Genetics Unit, Shriners Hospital for Children Montréal, Québec H3G 1A6, Canada.
Gauthier
Claude
C
Hannigan
Gregory E
GE
Dedhar
Shoukat
S
St-Arnaud
René
R
D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000201:enzymology*; D002522:Chlorocebus aethiops; D018076:DNA, Complementary / Q000235:genetics; D007700:Kinetics; D018832:Molecular Chaperones; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D000099200:Scaffold Protein ILK
D018076:DNA, Complementary; D018832:Molecular Chaperones; D010768:Phosphoserine; D017346:Protein Serine-Threonine Kinases; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D015534:Trans-Activators; D000099200:Scaffold Protein ILK; C096099:nascent-polypeptide-associated complex