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.