Role of protein oligomerization in regulation of Wnt target gene transcription.

摘要

Wnt/Wg signaling is a highly conserved signaling pathway that is important for animal development and adult homeostasis. There are so many aspects of the pathway that are not well understood, and transcriptional regulation is one of them. TCF is a DNA binding mediator of signaling, and carries out transcriptional roles by associating with a variety of factors. Some of those repress Wg target genes in the absence of signaling, while some activate upon signal stimulation. One such factor is CtBP, which is both an activator and repressor of Wg targets. In this study, a mutational analysis revealed that the basis for this differential activity of CtBP is its ability to form oligomers. CtBP monomers are able to activate Wg targets, while their self-association into oligomers leads to repression of Wg targets. Furthermore, it was found that TCF can also self-associate. Some TCFs bind two different cis-elements termed HMG and Helper sites, in a bipartite manner. These sites have variable spacing and orientation and one attractive hypothesis is that oligmerization of TCF can overcome the requirement for a fixed spacing and orientation of these sites. Therefore, protein oligomerization plays crucial roles in regulating Wnt target gene transcription.