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Pja2 Inhibits Wnt/β-catenin Signaling by Reducing the Level of TCF/LEF1
Int J Stem Cells 2018;11:242-247
Published online November 30, 2018;  
© 2018 Korean Society for Stem Cell Research.

Yonghee Song1, Somyung Lee1, Jeong-Rae Kim2, Eek-hoon Jho1

1Department of Life Science, University of Seoul, Seoul, Korea
2Department of Mathematics, University of Seoul, Seoul, Korea
Correspondence to: Eek-hoon Jho
Department of Life Science, University of Seoul, 163, Seoulsiripdae-ro, Dongdaemun-gu, Seoul 02504, Korea
Tel: +82-2-6490-2671, Fax: +82-2-6490-2664
E-mail: ej70@uos.ac.kr
Received April 5, 2018; Revised June 13, 2018; Accepted June 14, 2018.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Ubiquitination of proteins plays an essential role in various cellular processes, including protein degradation, DNA repair, and cell signaling pathways. Previous studies have shown that protein ubiquitination is implicated in regulating pluripotency as well as fate determination of stem cells. To identify how protein ubiquitination affects differentiation of embryonic stem cells, we analyzed microarray data, which are available in the public domain, of E3 ligases and deubiquitinases whose levels changed during stem cell differentiation. Expression of pja2, a member of the RING-type E3 ligase family, was up-regulated during differentiation of stem cells. Wnt/β-catenin signaling is one of the most important signaling pathways for regulation of the self-renewal and differentiation of embryonic stem cells. Pja2 was shown to bind to TCF/LEF1, which are transcriptional factors for Wnt/β-catenin signaling, and regulate protein levels by ubiquitination, leading to down-regulation of Wnt signaling activity. Based on these results, we suggest that E3 ligase Pja2 regulates stem cell differentiation by controlling the level of TCF/LEF1 by ubiquitination.
Keywords : Pja2, E3 ligase, Wnt, TCF/LEF1, Embryonic stem cell, Differentiation


November 2018, 11 (2)