cAMP-dependent regulation of proenkephalin by JunD and JunB: positive and negative effects of AP-1 proteins.

Abstract

We demonstrate that JunD, a component of the AP-1 transcription factor complex, activates transcription of the human proenkephalin gene in a fashion that is completely dependent upon the cAMP-dependent protein kinase, protein kinase A. Activation of proenkephalin transcription by JunD is dependent upon a previously characterized cAMP-, phorbol ester-, and Ca(2+)-inducible enhancer, and JunD is shown to bind the enhancer as a homodimer. Another component of the AP-1 transcription complex, JunB, is shown to inhibit activation mediated by JunD. As a homodimer JunB is unable to bind the enhancer; however in the presence of c-Fos, high-affinity binding is observed. Furthermore, JunD is shown to activate transcription of genes linked to both cAMP and phorbol ester response elements in a protein kinase A-dependent fashion, further blurring the distinction between these response elements. These results demonstrate that the transcriptional activity of an AP-1-related protein is regulated by the cAMP-dependent second-messenger pathway and suggest that JunD and other AP-1-related proteins may play an important role in the regulation of gene expression by cAMP-dependent intracellular signaling pathways.

Signal transduction from the extracellular matrix.

“…Both positive and negative cooperation between induced and constitutive factors may be involved in gene regulation (69,91). In addition, the same enhancer element (AP-1, for example) may be the site of both positive and negative regulation (28,75). Although the nuclear translocation of NF-kB is associated with adhesion to plastic (48), adherence to ECM ligands that provide specificity of gene induction is likely to induce the nuclear association of additional positive and/or negative transcription factors, not seen through direct integrin engagement or adhesion to plastic.…”

Transcriptional Control of Gene Expression by cAMP‐Response Element Binding Proteins

“…Two bZip transcription factors, ATF-3 and JunD (a member of the Jun/Fos family of proteins), form heterodimers and activate CAMP-dependent transcription of the proenkephalin gene (69,70). ATF-3 also forms heterodimers with ATF-2 (92) has not yet been established whether JunD and ATF-3 are substrates of PKA.…”

Molecular mechanisms of stress-induced proenkephalin gene regulation: CREB interacts with the proenkephalin gene in the mouse hypothalamus and is phosphorylated in response to hyperosmolar stress

“…The DNA elements within the human proenkephalin gene that confer responsiveness to second messengers and membrane depolarization have been well characterized (1)(2)(3)(4)(5)(6)(7)(8). To obtain uniform cells for transfection, however, the critical studies of transcriptional mechanism have largely used transformed cell lines (1-7), rather than tissues in vivo.…”