ZFIN ID: ZDB-PUB-061020-30
Adenomatous polyposis coli control of C-terminal binding protein-1 stability regulates expression of intestinal retinol dehydrogenases
Nadauld, L.D., Phelps, R., Moore, B.C., Eisinger, A., Sandoval, I.T., Chidester, S., Peterson, P.W., Manos, E.J., Sklow, B., Burt, R.W., and Jones, D.A.
Date: 2006
Source: The Journal of biological chemistry   281(49): 37828-37835 (Journal)
Registered Authors:
Keywords: none
MeSH Terms:
  • Adenoma/genetics
  • Adenoma/metabolism
  • Adenomatous Polyposis Coli/genetics
  • Adenomatous Polyposis Coli/metabolism
  • Alcohol Oxidoreductases/antagonists & inhibitors
  • Alcohol Oxidoreductases/genetics
  • Alcohol Oxidoreductases/metabolism*
  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Colonic Neoplasms/genetics
  • Colonic Neoplasms/metabolism
  • DNA-Binding Proteins/antagonists & inhibitors
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism*
  • Genes, APC*
  • Humans
  • In Vitro Techniques
  • Intestines/metabolism*
  • Models, Biological
  • Mutation
  • Proteasome Endopeptidase Complex/metabolism
  • RNA, Small Interfering/genetics
  • Species Specificity
  • Tretinoin/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • beta Catenin/antagonists & inhibitors
  • beta Catenin/genetics
  • beta Catenin/metabolism
PubMed: 17028196 Full text @ J. Biol. Chem.
Mutations in the human adenomatous polyposis coli (APC) gene are thought to initiate colorectal tumorigenesis. The tumor suppressor function of APC is attributed primarily to its ability to regulate the WNT pathway by targeting the destruction of ss-catenin. We report here a novel role for APC in regulating degradation of the transcriptional co-repressor c-terminal binding protein-1 (CtBP1) through a proteasome-dependent process. Further, CtBP1 suppresses the expression of intestinal retinol dehydrogenases, which are required for retinoic acid production and intestinal differentiation. In support of a role for CtBP1 in initiation of colorectal cancer, adenomas taken from individuals with familial adenomatous polyposis contain high levels of CtBP1 protein in comparison to matched, uninvolved tissue. The relationship between APC and CtBP1 is conserved between humans and zebrafish and provides a mechanistic model explaining APC control of intestinal retinoic acid biosynthesis.