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CRL4Mahj E3 ubiquitin ligase promotes neural stem cell reactivation.

Publication ,  Journal Article
Ly, PT; Tan, YS; Koe, CT; Zhang, Y; Xie, G; Endow, S; Deng, W-M; Yu, F; Wang, H
Published in: PLoS Biol
June 2019

The ability of neural stem cells (NSCs) to transit between quiescence and proliferation is crucial for brain development and homeostasis. Drosophila Hippo pathway maintains NSC quiescence, but its regulation during brain development remains unknown. Here, we show that CRL4Mahj, an evolutionarily conserved E3 ubiquitin ligase, is essential for NSC reactivation (exit from quiescence). We demonstrate that damaged DNA-binding protein 1 (DDB1) and Cullin4, two core components of Cullin4-RING ligase (CRL4), are intrinsically required for NSC reactivation. We have identified a substrate receptor of CRL4, Mahjong (Mahj), which is necessary and sufficient for NSC reactivation. Moreover, we show that CRL4Mahj forms a protein complex with Warts (Wts/large tumor suppressor [Lats]), a kinase of the Hippo signaling pathway, and Mahj promotes the ubiquitination of Wts. Our genetic analyses further support the conclusion that CRL4Mahj triggers NSC reactivation by inhibition of Wts. Given that Cullin4B mutations cause mental retardation and cerebral malformation, similar regulatory mechanisms may be applied to the human brain.

Duke Scholars

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Published In

PLoS Biol

DOI

EISSN

1545-7885

Publication Date

June 2019

Volume

17

Issue

6

Start / End Page

e3000276

Location

United States

Related Subject Headings

  • Ubiquitination
  • Ubiquitin-Protein Ligases
  • Ubiquitin-Protein Ligase Complexes
  • Signal Transduction
  • Protein Binding
  • Neural Stem Cells
  • Humans
  • Drosophila melanogaster
  • Drosophila Proteins
  • Developmental Biology
 

Citation

APA
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MLA
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Ly, P. T., Tan, Y. S., Koe, C. T., Zhang, Y., Xie, G., Endow, S., … Wang, H. (2019). CRL4Mahj E3 ubiquitin ligase promotes neural stem cell reactivation. PLoS Biol, 17(6), e3000276. https://doi.org/10.1371/journal.pbio.3000276
Ly, Phuong Thao, Ye Sing Tan, Chwee Tat Koe, Yingjie Zhang, Gengqiang Xie, Sharyn Endow, Wu-Min Deng, Fengwei Yu, and Hongyan Wang. “CRL4Mahj E3 ubiquitin ligase promotes neural stem cell reactivation.PLoS Biol 17, no. 6 (June 2019): e3000276. https://doi.org/10.1371/journal.pbio.3000276.
Ly PT, Tan YS, Koe CT, Zhang Y, Xie G, Endow S, et al. CRL4Mahj E3 ubiquitin ligase promotes neural stem cell reactivation. PLoS Biol. 2019 Jun;17(6):e3000276.
Ly, Phuong Thao, et al. “CRL4Mahj E3 ubiquitin ligase promotes neural stem cell reactivation.PLoS Biol, vol. 17, no. 6, June 2019, p. e3000276. Pubmed, doi:10.1371/journal.pbio.3000276.
Ly PT, Tan YS, Koe CT, Zhang Y, Xie G, Endow S, Deng W-M, Yu F, Wang H. CRL4Mahj E3 ubiquitin ligase promotes neural stem cell reactivation. PLoS Biol. 2019 Jun;17(6):e3000276.
Journal cover image

Published In

PLoS Biol

DOI

EISSN

1545-7885

Publication Date

June 2019

Volume

17

Issue

6

Start / End Page

e3000276

Location

United States

Related Subject Headings

  • Ubiquitination
  • Ubiquitin-Protein Ligases
  • Ubiquitin-Protein Ligase Complexes
  • Signal Transduction
  • Protein Binding
  • Neural Stem Cells
  • Humans
  • Drosophila melanogaster
  • Drosophila Proteins
  • Developmental Biology