Oct-3/4 regulates stem cell identity and cell fate decisions by modulating Wnt/β-catenin signalling

Monther Abu-Remaileh, Ariela Gerson, Marganit Farago, Gili Nathan, Irit Alkalay, Sharon Zins Rousso, Michal Gur, Abraham Fainsod, Yehudit Bergman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Although the transcriptional regulatory events triggered by Oct-3/4 are well documented, understanding the proteomic networks that mediate the diverse functions of this POU domain homeobox protein remains a major challenge. Here, we present genetic and biochemical studies that suggest an unexpected novel strategy for Oct-3/4-dependent regulation of embryogenesis and cell lineage determination. Our data suggest that Oct-3/4 specifically interacts with nuclear β-catenin and facilitates its proteasomal degradation, resulting in the maintenance of an undifferentiated, early embryonic phenotype both in Xenopus embryos and embryonic stem (ES) cells. Our data also show that Oct-3/4-mediated control of β-catenin stability has an important function in regulating ES cell motility. Down-regulation of Oct-3/4 increases β-catenin protein levels, enhancing Wnt signalling and initiating invasive cellular activity characteristic of epithelial-mesenchymal transition. Our data suggest a novel mode of regulation by which a delicate balance between β-catenin, Tcf3 and Oct-3/4 regulates maintenance of stem cell identity. Altering the balance between these proteins can direct cell fate decisions and differentiation.

Original languageAmerican English
Pages (from-to)3236-3248
Number of pages13
JournalEMBO Journal
Volume29
Issue number19
DOIs
StatePublished - 6 Oct 2010

Keywords

  • ES cells
  • Oct-3/4
  • Tcf3
  • β-catenin

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