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Title: Deubiquitinating enzymes regulate Hes1 stability and neuronal differentiation.
Authors: Kobayashi, Taeko  kyouindb  KAKEN_id
Iwamoto, Yumiko
Takashima, Kazuhiro
Isomura, Akihiro  kyouindb  KAKEN_id
Kosodo, Yoichi
Kawakami, Koichi
Nishioka, Tomoki
Kaibuchi, Kozo
Kageyama, Ryoichiro  kyouindb  KAKEN_id  orcid (unconfirmed)
Author's alias: 小林, 妙子
Keywords: basic helix-loop-helix transcription factor (bHLH)
Issue Date: 23-Apr-2015
Publisher: wiley
Journal title: The FEBS journal
Volume: 282
Issue: 13
Start page: 2411
End page: 2423
Abstract: Hairy and enhancer of split 1 (Hes1), a basic helix-loop-helix transcriptional repressor protein, regulates the maintenance of neural stem/progenitor cells by repressing proneural gene expression via Notch signaling. Previous studies showed that Hes1 expression oscillates in both mouse embryonic stem cells and neural stem cells, and that the oscillation contributes to their potency and differentiation fates. This oscillatory expression depends on the stability of Hes1, which is rapidly degraded by the ubiquitin/proteasome pathway. However, the detailed molecular mechanisms governing Hes1 stability remain unknown. We analyzed Hes1-interacting deubiquitinases purified from mouse embryonic stem cells using an Hes1-specific antibody, and identified the ubiquitin-specific protease 27x (Usp27x) as a new regulator of Hes1. We found that Hes1 was deubiquitinated and stabilized by Usp27x and its homologs ubiquitin-specific protease 22 (Usp22) and ubiquitin-specific protease 51 (Usp51). Knockdown of Usp22 shortened the half-life of Hes1, delayed its oscillation, and enhanced neuronal differentiation in mouse developing brain, whereas mis-expression of Usp27x reduced neuronal differentiation. These results suggest that these deubiquitinases modulate Hes1 protein dynamics by removing ubiquitin molecules, and thereby regulate neuronal differentiation of stem cells.
Rights: © 2015 The Authors. FEBS Journal published by John Wiley & Sons Ltd on behalf of FEBS.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
DOI(Published Version): 10.1111/febs.13290
PubMed ID: 25846153
Appears in Collections:Journal Articles

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