The ubiquitin ligase Huwe1 regulates the maintenance and lymphoid commitment of hematopoietic stem cells Journal Article


Authors: King, B.; Boccalatte, F.; Moran-Crusio, K.; Wolf, E.; Wang, J. J.; Kayembe, C.; Lazaris, C.; Yu, X. F.; Aranda-Orgilles, B.; Lasorella, A.; Aifantis, I.
Article Title: The ubiquitin ligase Huwe1 regulates the maintenance and lymphoid commitment of hematopoietic stem cells
Abstract: 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. We identified the ubiquitin ligase Huwe1 as a crucial regulator of HSC function via its post translational control of the oncoprotein N-myc (encoded by Mycn). We found Huwe1 to be essential for HSC self-renewal, quiescence and lymphoid-fate specification in mice. Through the use of a fluorescent fusion allele (Mycn(M)), we observed that N-myc expression was restricted to the most immature, multipotent stem and progenitor populations. N-myc expression was upregulated in response to stress or following loss of Huwel, which led to increased proliferation and stem-cell exhaustion. Mycn depletion reversed most of these phenotypes in vivo, which suggested that the attenuation of N-myc by Huwe1 is essential for reestablishing homeostasis following stress.
Keywords: phosphorylation; proliferation; quiescence; differentiation; n-myc; activation; tumor-suppressor; alpha; stability; c-myc protein
Journal Title: Nature Immunology
Volume: 17
Issue: 11
ISSN: 1529-2908
Publisher: Nature Publishing Group  
Date Published: 2016-11-01
Start Page: 1312
End Page: 1321
Language: English
ACCESSION: WOS:000386193200011
DOI: 10.1038/ni.3559
PROVIDER: wos
PMCID: PMC5117833
PUBMED: 27668798
Notes: Article -- Source: Wos
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  1. Bryan Christopher King
    11 King