Cell cycle-dependent variations in c-Jun and JunB phosphorylation: a role in the control of cyclin D1 expression.
The transcription factor AP-1, composed of Jun and Fos proteins, is a major target of mitogen-activated signal transduction pathways. However, little is known about AP-1 function in normal cycling cells. Here we report that the quantity and the phosphorylation state of the c-Jun and JunB proteins vary at the M-G(1) transition. Phosphorylation of JunB by the p34(cdc2)-cyclin B kinase is associated with lower JunB protein levels in mitotic and early G(1) cells. In contrast, c-Jun levels remain constant while the protein undergoes N-terminal phosphorylation, increasing its transactivation potential. Since JunB represses and c-Jun activates the cyclin D1 promoter, these modifications of AP-1 activity during the M-G(1) transition could provide an impetus for G(1) progression by a temporal increase in cyclin D1 transcription. These findings constitute a novel example of a reciprocal connection between transcription factors and the cell cycle machinery.
Bakiri
L
L
Unité des Virus Oncogènes, URA CNRS 1644, Institut Pasteur, 25, Rue du Dr Roux, 75724 Paris Cedex 15, France.
Lallemand
D
D
Bossy-Wetzel
E
E
Yaniv
M
M
D000818:Animals; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D019926:Cyclin B / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016193:G1 Phase; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008938:Mitosis; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection
D019926:Cyclin B; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D019938:Cyclin D1; D016203:CDC2 Protein Kinase