VARIATIONS IN JUN AND FOS PROTEIN EXPRESSION AND AP-1 ACTIVITY IN CYCLING, RESTING AND STIMULATED FIBROBLASTS

We have analysed the different Jun and Fos proteins as NIH3T3 fibrobla sts pass from exponential growth to quiescence and during the first 24 h after their re-entry into the cell cycle following serum stimulatio n, We show that these proteins can be divided into 3 subgroups based o n their pattern of expression. The first contains c-Jun, Jun-D and Fra -2 which are expressed at high level in cycling cells and are only mil dly induced by serum. The second contains Jun-B, c-Fos, Fos-B and Delt a Fos-B whose levels are low in cycling cells but increase strongly an d rapidly after stimulation by serum. The third group contains only Fr a-1, which is absent from cycling cells and behaves as a delayed early response protein after serum stimulation, AP-I binding activity is lo w both in cycling and quiescent fibroblasts but increases after stimul ation by serum with kinetics matching the induction of the various Jun and Fos proteins. Antibody supershift analyses demonstrate that the c omposition of AP-I binding activity reflects the relative abundance of each Jun and Fos protein. Furthermore, the state of post-translationa l modification varies continuously for all of the AP-1 proteins as gro wth conditions change. These data indicate that AP-1 activity during t he G(0)-G(1) transition is finely regulated and complex, involving cha nges both in protein expression and in posttranslational modification.