Promoter-specific ¿raws-Activationand Inhibition Mediated by .limit

Nuclear levels of c-Jun, .limit. c-Fos, and LRF-1 (liver regeneration factor) are high for a large fraction of the G| phase in regenerating liver and mitogen-stimulated hepatic cells. Previously, .limit was regarded as a less potent transcriptional activator than c-Jun that could also function as a represser. However, we found that, like c-Jun, .limit alone or LRF-1/ .limit strongly transactivates a cAMP-responsive promoter. Unlike c-Jun, .limit represses several AP-1 or activator of transcription factor sitecontaining promoters, and this inhibition is greatly enhanced in the pres ence of LRF-1. Here, we identify separate regions of .limit required for franv-aclivation and repression of these promoters. Deletion analysis shows that the region involved in /ran.v-activation function is highly con served among all Jun family members and corresponds to activator do main (Al) of c-Jun. In contrast, repression is maximal in the presence of both the DNA-binding domain and a region proximal to the basic region that is highly divergent among Jun proteins. Functional distinctions be tween Jun proteins during induction of the growth response and tumorigenesis may be accounted for by promoter-specific activation and repres sion mediated by regional differences in Jun family proteins.