Deubiquitylase HAUSP stabilizes REST and promotes maintenance of neural progenitor cells

Zhi Huang, Qiulian Wu, Olga A. Guryanova, Lin Cheng, Weinian Shou, Jeremy N. Rich, Shideng Bao

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

The repressor element 1-silencing transcription factor (REST) functions as a master regulator to maintain neural stem/progenitor cells (NPCs). REST undergoes proteasomal degradation through β-TrCP-mediated ubiquitylation during neuronal differentiation. However, reciprocal mechanisms that stabilize REST in NPCs are undefined. Here we show that the deubiquitylase HAUSP counterbalances REST ubiquitylation and prevents NPC differentiation. HAUSP expression declines concordantly with REST on neuronal differentiation and reciprocally with β-TrCP levels. HAUSP knockdown in NPCs decreases REST and induces differentiation. In contrast, HAUSP overexpression upregulates REST by overriding β-TrCP-mediated ubiquitylation. A consensus site (310-PYSS-313) in human REST is required for HAUSP-mediated REST deubiquitylation. Furthermore, REST overexpression in NPCs rescues the differentiation phenotype induced by HAUSP knockdown. These data demonstrate that HAUSP stabilizes REST through deubiquitylation and antagonizes β-TrCP in regulating REST at the post-translational level. Thus, HAUSP-mediated deubiquitylation represents a critical regulatory mechanism involved in the maintenance of NPCs.

Original languageEnglish
Pages (from-to)142-152
Number of pages11
JournalNature Cell Biology
Volume13
Issue number2
DOIs
StatePublished - Feb 2011

Fingerprint

Transcriptional Silencer Elements
Transcription Factors
Stem Cells
Maintenance
Neural Stem Cells
Ubiquitination
Cell Differentiation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Huang, Z., Wu, Q., Guryanova, O. A., Cheng, L., Shou, W., Rich, J. N., & Bao, S. (2011). Deubiquitylase HAUSP stabilizes REST and promotes maintenance of neural progenitor cells. Nature Cell Biology, 13(2), 142-152. https://doi.org/10.1038/ncb2153

Deubiquitylase HAUSP stabilizes REST and promotes maintenance of neural progenitor cells. / Huang, Zhi; Wu, Qiulian; Guryanova, Olga A.; Cheng, Lin; Shou, Weinian; Rich, Jeremy N.; Bao, Shideng.

In: Nature Cell Biology, Vol. 13, No. 2, 02.2011, p. 142-152.

Research output: Contribution to journalArticle

Huang, Z, Wu, Q, Guryanova, OA, Cheng, L, Shou, W, Rich, JN & Bao, S 2011, 'Deubiquitylase HAUSP stabilizes REST and promotes maintenance of neural progenitor cells', Nature Cell Biology, vol. 13, no. 2, pp. 142-152. https://doi.org/10.1038/ncb2153
Huang, Zhi ; Wu, Qiulian ; Guryanova, Olga A. ; Cheng, Lin ; Shou, Weinian ; Rich, Jeremy N. ; Bao, Shideng. / Deubiquitylase HAUSP stabilizes REST and promotes maintenance of neural progenitor cells. In: Nature Cell Biology. 2011 ; Vol. 13, No. 2. pp. 142-152.
@article{d85ea2f40ae542c09d90f5a3fa42d974,
title = "Deubiquitylase HAUSP stabilizes REST and promotes maintenance of neural progenitor cells",
abstract = "The repressor element 1-silencing transcription factor (REST) functions as a master regulator to maintain neural stem/progenitor cells (NPCs). REST undergoes proteasomal degradation through β-TrCP-mediated ubiquitylation during neuronal differentiation. However, reciprocal mechanisms that stabilize REST in NPCs are undefined. Here we show that the deubiquitylase HAUSP counterbalances REST ubiquitylation and prevents NPC differentiation. HAUSP expression declines concordantly with REST on neuronal differentiation and reciprocally with β-TrCP levels. HAUSP knockdown in NPCs decreases REST and induces differentiation. In contrast, HAUSP overexpression upregulates REST by overriding β-TrCP-mediated ubiquitylation. A consensus site (310-PYSS-313) in human REST is required for HAUSP-mediated REST deubiquitylation. Furthermore, REST overexpression in NPCs rescues the differentiation phenotype induced by HAUSP knockdown. These data demonstrate that HAUSP stabilizes REST through deubiquitylation and antagonizes β-TrCP in regulating REST at the post-translational level. Thus, HAUSP-mediated deubiquitylation represents a critical regulatory mechanism involved in the maintenance of NPCs.",
author = "Zhi Huang and Qiulian Wu and Guryanova, {Olga A.} and Lin Cheng and Weinian Shou and Rich, {Jeremy N.} and Shideng Bao",
year = "2011",
month = "2",
doi = "10.1038/ncb2153",
language = "English",
volume = "13",
pages = "142--152",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Deubiquitylase HAUSP stabilizes REST and promotes maintenance of neural progenitor cells

AU - Huang, Zhi

AU - Wu, Qiulian

AU - Guryanova, Olga A.

AU - Cheng, Lin

AU - Shou, Weinian

AU - Rich, Jeremy N.

AU - Bao, Shideng

PY - 2011/2

Y1 - 2011/2

N2 - The repressor element 1-silencing transcription factor (REST) functions as a master regulator to maintain neural stem/progenitor cells (NPCs). REST undergoes proteasomal degradation through β-TrCP-mediated ubiquitylation during neuronal differentiation. However, reciprocal mechanisms that stabilize REST in NPCs are undefined. Here we show that the deubiquitylase HAUSP counterbalances REST ubiquitylation and prevents NPC differentiation. HAUSP expression declines concordantly with REST on neuronal differentiation and reciprocally with β-TrCP levels. HAUSP knockdown in NPCs decreases REST and induces differentiation. In contrast, HAUSP overexpression upregulates REST by overriding β-TrCP-mediated ubiquitylation. A consensus site (310-PYSS-313) in human REST is required for HAUSP-mediated REST deubiquitylation. Furthermore, REST overexpression in NPCs rescues the differentiation phenotype induced by HAUSP knockdown. These data demonstrate that HAUSP stabilizes REST through deubiquitylation and antagonizes β-TrCP in regulating REST at the post-translational level. Thus, HAUSP-mediated deubiquitylation represents a critical regulatory mechanism involved in the maintenance of NPCs.

AB - The repressor element 1-silencing transcription factor (REST) functions as a master regulator to maintain neural stem/progenitor cells (NPCs). REST undergoes proteasomal degradation through β-TrCP-mediated ubiquitylation during neuronal differentiation. However, reciprocal mechanisms that stabilize REST in NPCs are undefined. Here we show that the deubiquitylase HAUSP counterbalances REST ubiquitylation and prevents NPC differentiation. HAUSP expression declines concordantly with REST on neuronal differentiation and reciprocally with β-TrCP levels. HAUSP knockdown in NPCs decreases REST and induces differentiation. In contrast, HAUSP overexpression upregulates REST by overriding β-TrCP-mediated ubiquitylation. A consensus site (310-PYSS-313) in human REST is required for HAUSP-mediated REST deubiquitylation. Furthermore, REST overexpression in NPCs rescues the differentiation phenotype induced by HAUSP knockdown. These data demonstrate that HAUSP stabilizes REST through deubiquitylation and antagonizes β-TrCP in regulating REST at the post-translational level. Thus, HAUSP-mediated deubiquitylation represents a critical regulatory mechanism involved in the maintenance of NPCs.

UR - http://www.scopus.com/inward/record.url?scp=79551600613&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79551600613&partnerID=8YFLogxK

U2 - 10.1038/ncb2153

DO - 10.1038/ncb2153

M3 - Article

VL - 13

SP - 142

EP - 152

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 2

ER -