Fiche publication
Date publication
février 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DOMON-DELL Claire
,
Dr DULUC Isabelle
,
Dr FREUND Jean-Noël
,
Dr GROSS Isabelle
,
Pr REIMUND Jean-Marie
Tous les auteurs :
Freund JN, Duluc I, Reimund JM, Gross I, Domon-Dell C
Lien Pubmed
Résumé
The homeoprotein encoded by the intestinal-specific Cdx2 gene is a major regulator of gut development and homeostasis, also involved in colon cancer as well as in intestinal-type metaplasias when it is abnormally expressed outside the gut. At the molecular level, structure/function studies have demonstrated that the Cdx2 protein is a transcription factor containing a conserved homeotic DNA-binding domain made of three alpha helixes arranged in a helix-turn-helix motif, preceded by a transcriptional domain and followed by a regulatory domain. The protein interacts with several thousand sites on the chromatin and widely regulates intestinal functions in stem/progenitor cells as well as in mature differentiated cells. Yet, this transcription factor also acts trough original nontranscriptional mechanisms. Indeed, the identification of novel protein partners of Cdx2 and also of a splicing variant revealed unexpected functions in the control of signaling pathways like the Wnt and NF-kappaB pathways, in double-strand break DNA repair and in premessenger RNA splicing. These novel functions of Cdx2 must be considered to fully understand the complexity of the role of Cdx2 in the healthy intestine and in diseases.
Référence
World J Gastroenterol. 2015 Feb 7;21(5):1436-43
