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 t he quantity and the phosphorylation state of the c-Jun and JunB proteins va ry at the M-G(1) transition. Phosphorylation of JunB by the p34(cdc2)-cycli n B kinase is associated with lower JunB protein levels in mitotic and earl y G(1) cells, In contrast, c-Jun levels remain constant while the protein u ndergoes N-terminal phosphorylation, increasing its transactivation potenti al. 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 a n impetus for G(1) progression by a temporal increase in cyclin DI transcri ption. These findings constitute a novel example of a reciprocal connection between transcription factors and the cell cycle machinery.