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The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment

Hematopoietic stem cells (HSCs) are dormant in the bone marrow and can be activated in response to diverse stresses to replenish all blood cell types. Here we identify the ubiquitin ligase Huwe1 as a crucial regulator of HSC functions via its post-translational control of N-myc. We found Huwe1 to be...

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Autores principales: King, Bryan, Boccalatte, Francesco, Moran-Crusio, Kelly, Wolf, Elmar, Wang, Jingjing, Kayembe, Clarisse, Lazaris, Charalampos, Yu, Xiaofeng, Aranda-Orgilles, Beatriz, Lasorella, Anna, Aifantis, Iannis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5117833/
https://www.ncbi.nlm.nih.gov/pubmed/27668798
http://dx.doi.org/10.1038/ni.3559
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author King, Bryan
Boccalatte, Francesco
Moran-Crusio, Kelly
Wolf, Elmar
Wang, Jingjing
Kayembe, Clarisse
Lazaris, Charalampos
Yu, Xiaofeng
Aranda-Orgilles, Beatriz
Lasorella, Anna
Aifantis, Iannis
author_facet King, Bryan
Boccalatte, Francesco
Moran-Crusio, Kelly
Wolf, Elmar
Wang, Jingjing
Kayembe, Clarisse
Lazaris, Charalampos
Yu, Xiaofeng
Aranda-Orgilles, Beatriz
Lasorella, Anna
Aifantis, Iannis
author_sort King, Bryan
collection PubMed
description Hematopoietic stem cells (HSCs) are dormant in the bone marrow and can be activated in response to diverse stresses to replenish all blood cell types. Here we identify the ubiquitin ligase Huwe1 as a crucial regulator of HSC functions via its post-translational control of N-myc. We found Huwe1 to be essential for HSC self-renewal, quiescence and lymphoid fate specification. Using a novel fluorescent fusion allele (Mycn(M)), we observed that N-myc expression was restricted to the most immature, multipotent stem and progenitor populations. N-myc was upregulated in response to stress or upon loss of Huwe1, leading to increased proliferation and stem cell exhaustion. Mycn depletion reversed most of these phenotypes in vivo, suggesting that the attenuation of N-myc by Huwe1 is essential to reestablish homeostasis following stress.
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spelling pubmed-51178332017-03-26 The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment King, Bryan Boccalatte, Francesco Moran-Crusio, Kelly Wolf, Elmar Wang, Jingjing Kayembe, Clarisse Lazaris, Charalampos Yu, Xiaofeng Aranda-Orgilles, Beatriz Lasorella, Anna Aifantis, Iannis Nat Immunol Article Hematopoietic stem cells (HSCs) are dormant in the bone marrow and can be activated in response to diverse stresses to replenish all blood cell types. Here we identify the ubiquitin ligase Huwe1 as a crucial regulator of HSC functions via its post-translational control of N-myc. We found Huwe1 to be essential for HSC self-renewal, quiescence and lymphoid fate specification. Using a novel fluorescent fusion allele (Mycn(M)), we observed that N-myc expression was restricted to the most immature, multipotent stem and progenitor populations. N-myc was upregulated in response to stress or upon loss of Huwe1, leading to increased proliferation and stem cell exhaustion. Mycn depletion reversed most of these phenotypes in vivo, suggesting that the attenuation of N-myc by Huwe1 is essential to reestablish homeostasis following stress. 2016-09-26 2016-11 /pmc/articles/PMC5117833/ /pubmed/27668798 http://dx.doi.org/10.1038/ni.3559 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
King, Bryan
Boccalatte, Francesco
Moran-Crusio, Kelly
Wolf, Elmar
Wang, Jingjing
Kayembe, Clarisse
Lazaris, Charalampos
Yu, Xiaofeng
Aranda-Orgilles, Beatriz
Lasorella, Anna
Aifantis, Iannis
The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment
title The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment
title_full The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment
title_fullStr The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment
title_full_unstemmed The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment
title_short The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment
title_sort ubiquitin ligase huwe1 regulates hematopoietic stem cell maintenance and lymphoid commitment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5117833/
https://www.ncbi.nlm.nih.gov/pubmed/27668798
http://dx.doi.org/10.1038/ni.3559
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