Novel double-negative feedback loop between adenomatous polyposis coli and Musashi1 in colon epithelia

J Biol Chem. 2011 Feb 18;286(7):4946-50. doi: 10.1074/jbc.C110.205922. Epub 2011 Jan 3.

Abstract

Loss of tumor suppressor adenomatous polyposis coli (APC) is thought to initiate the majority of all colorectal cancers. The predominant theory of colorectal carcinogenesis implicates stem cells as the initiating cells. However, relatively little is known about the function of APC in governing the homeostasis of normal intestinal stem cells. Here, we identify a novel double-negative feedback loop between APC and a translation inhibitor protein, Musashi1 (MSI1), in cultured human colonocytes. We show APC as a key factor in MSI1 regulation through Wnt signaling and identify APC mRNA as a novel target of translational inhibition by MSI1. We propose that APC/MSI1 interactions maintain homeostatic balance in the intestinal epithelium.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics
  • Adenomatous Polyposis Coli Protein / metabolism*
  • Animals
  • Colon / cytology
  • Colon / metabolism*
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism*
  • Mice
  • NIH 3T3 Cells
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Biosynthesis / physiology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction / physiology*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism

Substances

  • APC protein, human
  • Adenomatous Polyposis Coli Protein
  • MSI1 protein, human
  • Msi1h protein, mouse
  • Nerve Tissue Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Wnt Proteins