Interaction of an approximately 40 kDa protein from regenerating rat liver with the -148 to -124 region of c-jun complexed with RLjunRP coincides with enhanced c-jun expression in proliferating rat liver.

The c-jun belongs to the family of proto-oncogenes and encodes for the protein Jun, a component of transcription factor AP-1 involved in regulation of the expression of genes indispensable for cell proliferation and differentiation. While the role of c-jun in the regulation of such genes has been well examined, the regulation of c-jun in proliferating cells is not fully understood. We have earlier reported that the -148 to -124 region of c-jun is involved in the positive regulation of c-jun transcription, and interacts with a positive regulatory factor (rat liver jun regulatory protein; RLjunRP) present in rat liver. In this investigation, we report that this region is differentially recognized in proliferating liver as evidenced by the formation of a complex, different from that observed with normal liver extract. The new complex appears as early as 2 h after partial hepatectomy and its appearance coincides with the rise in c-jun mRNA levels after partial hepatectomy. In regenerating rat liver nuclear extract, an additional protein of approximately 40 kDa (rRLjunRP) interacts with a pre-existing dimer of RLjunRP complexed with the -148 to -124 region of c-jun to form a slow-migrating complex. rRLjunRP appears to pre-exist in the cytosol and translocate to the nucleus as indicated by the continued presence of the retarded complex in nuclear extract prepared from partially hepatectomized rats treated with cycloheximide. UV crosslinking studies, South-Western blot analysis, SDS/PAGE of affinity-purified factor(s), and 2D-PAGE analysis clearly demonstrate that the additional factor induced in response to growth stimulus is an approximately 40 kDa, that binds with the dimer of RLjunRP and enhances the c-jun transcription.