Acquisition of SOX transcription factor specificity through protein-protein interaction, modulation of Wnt signalling and post-translational modification

SOX transcription factors contain a high mobility group (HMG) box that confers sequence-specific (in the case of SOX/TCF) DNA binding ability to the protein. SOX proteins are transcriptional regulators involved in diverse tissues and developmental processes. Based on protein sequence comparisons, the SOX family is divided into eight groups. SOX proteins belonging to the same group tend to have overlapping tissue expression profiles and are able to functionally substitute for one another. However, SOX proteins belonging to different groups often do not show redundant regulatory functions. To achieve their specific actions, SOX proteins rely on interactions with a wide variety of proteins. The choice of binding partners as well as post-translational modifications of SOX proteins confers target gene specificity to the HMG box proteins which otherwise have weak DNA binding specificity. SOX proteins also regulate signalling pathways, such as the Wnt pathway by interacting with β-catenin and/or TCF/LEF transcription factors, employing different mechanisms to achieve similar functional outcomes. Here we review extensively the SOX protein interactions with partner co-factors, the ability of SOX proteins to modulate Wnt signalling and the effect of post-translational modification of SOX proteins on their function.