Interaction between Hhex and SOX13 modulates Wnt/TCF activity

Marfil, Vanessa;Moya, Marta;Pierreux, Christophe;Castell, Jose V.;Bort, Roque;et.al.
(2010) Journal of Biological Chemistry — Vol. 285, n° 8, p. 5726-5737 (2010)

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Abstract
Fine-tuning of the Wnt/TCF pathway is crucial for multiple embryological processes, including liver development. Here we describe how the interaction between Hhex (hematopoietically expressed homeobox) and SOX13 (SRY-related high mobility group box transcription factor 13), modulates Wnt/TCF pathway activity. Hhex is a homeodomain factor expressed in multiple endoderm-derived tissues, like the liver, where it is essential for proper development. The pleiotropic expression of Hhex during embryonic development and its dual role as a transcriptional repressor and activator suggest the presence of different tissue-specific partners capable of modulating its activity and function. While searching for developmentally regulated Hhex partners, we set up a yeast two-hybrid screening using an E9.5-10.5 mouse embryo library and the N-terminal domain of Hhex as bait. Among the putative protein interactors, we selected SOX13 for further characterization. We found that SOX13 interacts directly with full-length Hhex, and we delineated the interaction domains within the two proteins. SOX13 is known to repress Wnt/TCF signaling by interacting with TCF1. We show that Hhex is able to block the SOX13-dependent repression of Wnt/TCF activity by displacing SOX13 from the SOX13.TCF1 complex. Moreover, Hhex de-repressed the Wnt/TCF pathway in the ventral foregut endoderm of cultured mouse embryos electroporated with a SOX13-expressing plasmid. We conclude that the interaction between Hhex and SOX13 may contribute to control Wnt/TCF signaling in the early embryo.
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Marfil, V., Moya, M., Pierreux, C., Castell, J. V., Lemaigre, F., Real, F. X., & Bort, R. (2010). Interaction between Hhex and SOX13 modulates Wnt/TCF activity. Journal of Biological Chemistry, 285(8), 5726-5737. https://doi.org/10.1074/jbc.M109.046649 (Original work published 2010)