title: Novel double-negative feedback loop between adenomatous polyposis coli and Musashi1 in colon epithelia.
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.
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045, USA.
authors.forename: Erick
authors.initials: E
authors.lastname: Spears
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Neufeld
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; C491297:MSI1 protein, human; C104786:Msi1h protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051153:Wnt Proteins