Characterization of novel Hhex partners: SOX13 and c-Myc. New mechanism for the regulation of Wnt/TCF and c-Myc pathways

Marfil Vives, Vanessa

Characterization of novel Hhex partners: SOX13 and c-Myc. New mechanism for the regulation of Wnt/TCF and c-Myc pathways

Document Type

Doctoral thesis
Published Version

Author

Marfil Vives, Vanessa

Director

Bort, Roque

Tutor

Real, Francisco X.

Publication Date

2010-07-22

Pages

184 p.

Citation

Marfil Vives, V. Characterization of novel Hhex partners: SOX13 and c-Myc. New mechanism for the regulation of Wnt/TCF and c-Myc pathways. Universitat Pompeu Fabra; 2010. handle: http://hdl.handle.net/10803/22701

This citation was generated automatically.

Doctoral program

Programa de doctorat en Biomedicina

Abstract

Hhex transcription factor is expressed in multiple endoderm-derived tissues, like the liver, where it is essential for proper development. The pleiotropic effect of Hhex in the embryo and its dual role as a transcriptional repressor/activator suggest the presence of different interaction partners capable of modulating its activity and function. In the current study we identified two new Hhex protein interactors: SOX13 and c-Myc. We show that Hhex interacts directly with SOX13. By doing so, Hhex sequesters SOX13 from the SOX13•TCF1 complex, overturning SOX13-dependent repression of the Wnt pathway. On the other hand, Hhex induces proliferation of non-tumorigenic human fibroblast through a Myc-dependent mechanism. Hhex and c-Myc interact directly upregulating Cyclin D1, a c-Myc target gene involved in cell cycle progression and proliferation. Elevation of Cyclin D1 might be the final effector of Hhex capacity to regulate cell proliferation.