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Review
. 2014 Sep 5;3(2):74-82.
eCollection 2014.

The Oct4 protein: more than a magic stemness marker

Dana Zeineddine  1 , Aya Abou Hammoud  2 , Mohamad Mortada  1 , Hélène Boeuf  3
Affiliations
Review

The Oct4 protein: more than a magic stemness marker

Dana Zeineddine et al. Am J Stem Cells. .

Abstract

The Oct4 protein, encoded by the Pou5f1 gene was the very first master gene, discovered 25 years ago, to be absolutely required for the stemness properties of murine and primate embryonic stem cells. This transcription factor, which has also been shown to be essential for somatic cell reprogrammation, displays various functions depending upon its level of expression and has been quoted as a "rheostat" gene. Oct4 protein is in complexes with many different partners and its activity depends upon fine post-translational modifications. This review aims at revisiting some properties of this protein, which has not yet delivered all its potentialities.

Keywords: Oct4/ Pou5f1; cancer stem cells; cell lineages; embryonic stem cells; pluripotency.

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Figures

Figure 1
Figure 1
LIF signaling and post-translational modifications of some stemness transcription factors. The maintenance of self-renewal and pluripotency in mESC is controlled by extrinsic signaling pathway (LIF) and intrinsic self-renewal factors (eg: Oct4, Sox2 and Nanog). LIF binds to its heterodimeric receptor which leads to the activation of receptor associated Janus kinases (JAKs) which phosphorylate receptor docking sites and Stat3 on tyrosine 705 (Tyr705). Then, dimers of Phospho-Stat3 translocate to the nucleus and activate the transcription of target genes that are essential for ES cell self-renewal (eg: Klf4, Klf5 which induces expression of Mras GTPase). The activated Stat3 leads also to expression of its own repressor like Socs3, which serves as a negative feedback signal. Phosphorylation, Ubiquitination, SUMOylation and Acetylation of Oct4, Sox2 and Nanog control protein activity, expression, and stability, which result in modulation of ESC self-renewal activity. S stands for “stabilization” of the protein. Arrow indicates “activation” while the line indicates “repression”.
Figure 2
Figure 2
Protein sequence alignment of mammalian OCT4 proteins. Protein sequences of the different mammalian proteins, retrieved from GenBank, have been aligned with the MultiAlign software [81]. The conserved ERK, PKA and SUMOylation sites are indicated.
See this image and copyright information in PMC

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