A potential role for c-jun in cell cycle progression through late G1 and S.

When the level of c-jun mRNA was analyzed in WI-38 human fibroblasts exciting short- and long-term quiescence, two peaks of c-jun mRNA accumulation were found. The first occurred one hour after stimulation and lasted three to five hours, whereas the second occurred at the G1/S border and was coupled to the time of entry to S phase rather than to the time of stimulation. The early peak is well documented and in agreement with the proposed role of c-Jun/AP-1 in mediating cellular responses to receptor-generated signals. The later peak, however, has not been previously reported. Additional follow-up studies showed that late G1/S expression was not solely a phenomenon of cells existing a quiescent state, nor was it restricted only to human cells. Gel retardation studies confirmed that there is AP-1 specific DNA binding activity in nuclear extracts isolated in late G1 and S phase, and that this AP-1 binding activity is due to the presence of Jun protein. An anti-Fos antibody was able to significantly decrease AB-1 binding activity in early G1 extracts, but had no effect on extracts isolated in late G1 and S phase, indicating that the complexes observed in late G1 and S phase are clearly different from those seen in early G1. These studies are among the first to suggest a functional dissociation of c-Jun from c-Fos. Our results identify a new, previously unreported role for c-Jun/AP-1 in regulation of cell cycle progression and mammalian cell growth.