Inhibitory activities of short linear motifs underlie Hox interactome specificity in vivo

摘要

In all animals, it is important that cells are correctly organised into tissues and organs. This organisation starts in the embryo, and cells are instructed to perform different roles depending on their position within the body. A family of proteins called the Hox proteins coordinates the organisation of the cells in the animal embryo by binding to and controlling the expression of specific genes. To properly control their target genes, Hox proteins need to interact with other proteins called transcription factors that can also bind to the genes. However, only a few of these transcription factors have been identified so far, and it is not clear how Hox proteins are able to interact with them. Here, Ba?za, Viala, Heim et al. identified several more transcription factors that can bind to the Hox proteins in fruit fly embryos. The experiments show that Hox proteins are able to bind to many transcription factors that are very different from each other. Ba?za, Viala, Heim et al. also show that two short sections within the Hox proteins known as short linear motifs are important for controlling these interactions. A fly Hox protein that was missing these motifs was able to interact with new transcription factors. This inhibitory role was found in Hox proteins from mice and sea anemones, suggesting that these motifs may play the same role in all animals. Ba?za, Viala, Heim et al.'s findings challenge the traditional view of the role of the short linear motifs in interactions between proteins. Also, the findings provide an alternative explanation for how the Hox proteins are only able to interact with particular transcription factors in animal embryos. The next step will be to find out whether the inhibitory role of short linear motifs could more generally apply to many other protein families.