Transcriptional coactivators potentiating AP-1 function in bone.

Abstract

The AP-1 proteins are formed by the heterodimerization of Fos family members and Jun family members through a structural motif called the leucine zipper. The heterodimer can then bind DNA at a consensus site termed the AP-1 site and act as a transcription factor to modulate the expression of AP-1-responsive genes. All the Jun family members can also homodimerize to exert the same function. Genetic studies including gain-of-function and loss-of-function mutations have shown that AP-1 components, particularly the c-Fos protein, are essential for proper bone development. Both Fos and Jun family members interact with coactivator molecules to activate transcription. To date, the coactivator proteins CBP (CREB-binding protein), JAB1 (Jun-activation domain-binding protein 1), and alpha-NAC (Nascent polypeptide associated complex And Coactivator alpha) have been shown to potentiate the AP-1 transcriptional activating function. We have shown that all three proteins are expressed in bone during mouse development. These findings raise the intriguing possibility that multiple coactivators may be involved in mediating AP-1-dependent transcription and increase the specificity of target gene activation by AP-1 proteins in differentiating bone cells.