Jab1 co-activation of c-Jun is abrogated by the serine 10-phosphorylated form of p27Kip1.
The cyclin-dependent kinase (cdk) inhibitor p27(Kip1) is a central mediator in the imposition and maintenance of quiescence through the sequestration of G(1)-specific cyclin-cdk complexes. Previous studies have implicated the c-Jun co-activator protein Jab1 as a regulator of intracellular p27(Kip1) levels. Jab1 has been reported to interact with p27(Kip1) and cause its translocation to the cytoplasm as a prelude to the degradation of the cdk inhibitor. Here we describe experiments that showing phosphorylation of p27(Kip1) at serine 10 leads to the suppression of Jab1 levels with the concomitant inhibition of c-Jun-dependent transcription. This repression is minimized upon quiescence exit through the rapid and preferential loss of the serine 10-phosphorylated form of p27(Kip1) following serum stimulation. Our results, therefore, demonstrate an additional role for p27(Kip1) in the modulation of c-Jun-dependent transcription via Jab1.
Department of Biological Sciences, Imperial College of Science, Technology and Medicine, Exhibition Road, South Kensington, London, United Kingdom.
Shalu
S
Chopra
Silvia
S
Fernandez De Mattos
Eric W-F
EW
Lam
David J
DJ
Mann
D016475:3T3 Cells; D000818:Animals; D000075686:COP9 Signalosome Complex; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D004789:Enzyme Activation; D006801:Humans; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D010447:Peptide Hydrolases; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D012694:Serine; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; C501490:Cops5 protein, mouse; D000075686:COP9 Signalosome Complex