title: Extending the functions of the homeotic transcription factor Cdx2 in the digestive system through nontranscriptional activities.
abstract: 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-κB 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.
authors: Jean-Noël Freund, Isabelle Duluc, Jean-Marie Reimund, Isabelle Gross, Claire Domon-Dell, INSERM UMR_S1113, Université de Strasbourg, FMTS, 67200 Strasbourg, France.
authors: Jean-Noël
authors: JN
authors: Freund
authors: Jean-Noël Freund, Isabelle Duluc, Jean-Marie Reimund, Isabelle Gross, Claire Domon-Dell, INSERM UMR_S1113, Université de Strasbourg, FMTS, 67200 Strasbourg, France.
authors: Isabelle
authors: I
authors: Duluc
authors: Jean-Noël Freund, Isabelle Duluc, Jean-Marie Reimund, Isabelle Gross, Claire Domon-Dell, INSERM UMR_S1113, Université de Strasbourg, FMTS, 67200 Strasbourg, France.
authors: Jean-Marie
authors: JM
authors: Reimund
authors: Jean-Noël Freund, Isabelle Duluc, Jean-Marie Reimund, Isabelle Gross, Claire Domon-Dell, INSERM UMR_S1113, Université de Strasbourg, FMTS, 67200 Strasbourg, France.
authors: Isabelle
authors: I
authors: Gross
authors: Jean-Noël Freund, Isabelle Duluc, Jean-Marie Reimund, Isabelle Gross, Claire Domon-Dell, INSERM UMR_S1113, Université de Strasbourg, FMTS, 67200 Strasbourg, France.
authors: Claire
authors: C
authors: Domon-Dell
mesh_terms: D000818:Animals; D000071616:CDX2 Transcription Factor; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000473:pathology; D007422:Intestines / Q000473:pathology; D011487:Protein Conformation; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins
keywords: Cancer; DNA repair; Development; Homeobox; Homeostasis; Intestine; RNA splicing; Signaling; Transcription