REGULATION OF TRANSACTIVATING CAPACITY OF CRE-BPA BY PHORBOL ESTER TUMOR PROMOTER TPA

CRE-BPa, here designated as CRE-BPaalpha, is a novel member of the CRE (cAMP response element)-binding protein CRE-BP1 family. CRE-BPaalpha has four regions highly homologous to CRE-BP1, including a putative me tal finger structure and a DNA-binding domain consisting of a basic am ino acid cluster and a leucine zipper. CRE-BPa specifically binds to C RE as a homodimer or heterodimer with c-Jun or CRE-BP1. Here we report three alternative splicing forms of CRE-BPaalpha: two of them, CRE-BP abeta and CRE-BPagamma, lack the N-terminal 7 and 33 amino acids of CR E-BPaalpha, and the third one CRE-BPadelta, has 16 additional amino ac ids in the N-terminus and amino acids 156-508 of CRE-BPaalpha. In CAT cotransfection experiments using CV-1 cells, transient expression of e ach of four CRE-BPa proteins caused a 1.6- to 3.4-fold increase of CRE -dependent transcription, respectively. Interestingly, these weak tran s-activating capacities of CRE-BPa proteins were enhanced 2.7- to 3.6- fold by treatment of cells with 12-0-tetradecanoyl-phorbol 13-acetate (TPA). However, CRE-BPa did not affect the TPA-induced and TRE (TPA re sponse element)-dependent transcription. These results indicate that C RE-BPa is a CRE-dependent trans-activator, and that CRE-BPa can confer TPA inducibility on CRE. Thus, CRE-BPa has an unique characteristic o f cross-talk between cAMP pathway and TPA pathway.