Cargando…

Hematopoietic Stem Cell Differentiation Regulated by a Single Ubiquitin Ligase: Substrate Complex

Hematopoietic stem cell (HSC) differentiation is regulated by cell-intrinsic and extrinsic cues. In addition to transcriptional regulation, post-translational regulation may also control HSC differentiation. To test this hypothesis, we visualized ubiquitin-regulated protein stability of a single tra...

Descripción completa

Detalles Bibliográficos
Autores principales: Reavie, Linsey, Gatta, Giusy Della, Crusio, Kelly, Aranda-Orgilles, Beatriz, Buckley, Shannon M., Thompson, Benjamin, Lee, Eugine, Gao, Jie, Bredemeyer, Andrea L., Helmink, Beth A., Zavadil, Jiri, Sleckman, Barry P., Palomero, Teresa, Ferrando, Adolfo, Aifantis, Iannis
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825759/
https://www.ncbi.nlm.nih.gov/pubmed/20081848
http://dx.doi.org/10.1038/ni.1839
_version_ 1782177834576379904
author Reavie, Linsey
Gatta, Giusy Della
Crusio, Kelly
Aranda-Orgilles, Beatriz
Buckley, Shannon M.
Thompson, Benjamin
Lee, Eugine
Gao, Jie
Bredemeyer, Andrea L.
Helmink, Beth A.
Zavadil, Jiri
Sleckman, Barry P.
Palomero, Teresa
Ferrando, Adolfo
Aifantis, Iannis
author_facet Reavie, Linsey
Gatta, Giusy Della
Crusio, Kelly
Aranda-Orgilles, Beatriz
Buckley, Shannon M.
Thompson, Benjamin
Lee, Eugine
Gao, Jie
Bredemeyer, Andrea L.
Helmink, Beth A.
Zavadil, Jiri
Sleckman, Barry P.
Palomero, Teresa
Ferrando, Adolfo
Aifantis, Iannis
author_sort Reavie, Linsey
collection PubMed
description Hematopoietic stem cell (HSC) differentiation is regulated by cell-intrinsic and extrinsic cues. In addition to transcriptional regulation, post-translational regulation may also control HSC differentiation. To test this hypothesis, we visualized ubiquitin-regulated protein stability of a single transcription factor, c-Myc. The stability of c-Myc protein was instructive of HSC quiescence and c-Myc protein abundance was controlled by the ubiquitin ligase Fbw7. Fine changes in stability of c-Myc protein regulated the HSC “gene expression signature”. Using whole genome genomic approaches, we identified specific regulators of HSC function that are directly controlled by c-Myc binding, however adult HSCs and embryonic stem cells sense and interpret distinctly c-Myc regulated gene expression. These studies show a ubiquitin ligase substrate pair can orchestrate the molecular program of HSC differentiation.
format Text
id pubmed-2825759
institution National Center for Biotechnology Information
language English
publishDate 2010
record_format MEDLINE/PubMed
spelling pubmed-28257592010-09-01 Hematopoietic Stem Cell Differentiation Regulated by a Single Ubiquitin Ligase: Substrate Complex Reavie, Linsey Gatta, Giusy Della Crusio, Kelly Aranda-Orgilles, Beatriz Buckley, Shannon M. Thompson, Benjamin Lee, Eugine Gao, Jie Bredemeyer, Andrea L. Helmink, Beth A. Zavadil, Jiri Sleckman, Barry P. Palomero, Teresa Ferrando, Adolfo Aifantis, Iannis Nat Immunol Article Hematopoietic stem cell (HSC) differentiation is regulated by cell-intrinsic and extrinsic cues. In addition to transcriptional regulation, post-translational regulation may also control HSC differentiation. To test this hypothesis, we visualized ubiquitin-regulated protein stability of a single transcription factor, c-Myc. The stability of c-Myc protein was instructive of HSC quiescence and c-Myc protein abundance was controlled by the ubiquitin ligase Fbw7. Fine changes in stability of c-Myc protein regulated the HSC “gene expression signature”. Using whole genome genomic approaches, we identified specific regulators of HSC function that are directly controlled by c-Myc binding, however adult HSCs and embryonic stem cells sense and interpret distinctly c-Myc regulated gene expression. These studies show a ubiquitin ligase substrate pair can orchestrate the molecular program of HSC differentiation. 2010-01-17 2010-03 /pmc/articles/PMC2825759/ /pubmed/20081848 http://dx.doi.org/10.1038/ni.1839 Text en Users may view, print, copy, download and 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
Reavie, Linsey
Gatta, Giusy Della
Crusio, Kelly
Aranda-Orgilles, Beatriz
Buckley, Shannon M.
Thompson, Benjamin
Lee, Eugine
Gao, Jie
Bredemeyer, Andrea L.
Helmink, Beth A.
Zavadil, Jiri
Sleckman, Barry P.
Palomero, Teresa
Ferrando, Adolfo
Aifantis, Iannis
Hematopoietic Stem Cell Differentiation Regulated by a Single Ubiquitin Ligase: Substrate Complex
title Hematopoietic Stem Cell Differentiation Regulated by a Single Ubiquitin Ligase: Substrate Complex
title_full Hematopoietic Stem Cell Differentiation Regulated by a Single Ubiquitin Ligase: Substrate Complex
title_fullStr Hematopoietic Stem Cell Differentiation Regulated by a Single Ubiquitin Ligase: Substrate Complex
title_full_unstemmed Hematopoietic Stem Cell Differentiation Regulated by a Single Ubiquitin Ligase: Substrate Complex
title_short Hematopoietic Stem Cell Differentiation Regulated by a Single Ubiquitin Ligase: Substrate Complex
title_sort hematopoietic stem cell differentiation regulated by a single ubiquitin ligase: substrate complex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825759/
https://www.ncbi.nlm.nih.gov/pubmed/20081848
http://dx.doi.org/10.1038/ni.1839
work_keys_str_mv AT reavielinsey hematopoieticstemcelldifferentiationregulatedbyasingleubiquitinligasesubstratecomplex
AT gattagiusydella hematopoieticstemcelldifferentiationregulatedbyasingleubiquitinligasesubstratecomplex
AT crusiokelly hematopoieticstemcelldifferentiationregulatedbyasingleubiquitinligasesubstratecomplex
AT arandaorgillesbeatriz hematopoieticstemcelldifferentiationregulatedbyasingleubiquitinligasesubstratecomplex
AT buckleyshannonm hematopoieticstemcelldifferentiationregulatedbyasingleubiquitinligasesubstratecomplex
AT thompsonbenjamin hematopoieticstemcelldifferentiationregulatedbyasingleubiquitinligasesubstratecomplex
AT leeeugine hematopoieticstemcelldifferentiationregulatedbyasingleubiquitinligasesubstratecomplex
AT gaojie hematopoieticstemcelldifferentiationregulatedbyasingleubiquitinligasesubstratecomplex
AT bredemeyerandreal hematopoieticstemcelldifferentiationregulatedbyasingleubiquitinligasesubstratecomplex
AT helminkbetha hematopoieticstemcelldifferentiationregulatedbyasingleubiquitinligasesubstratecomplex
AT zavadiljiri hematopoieticstemcelldifferentiationregulatedbyasingleubiquitinligasesubstratecomplex
AT sleckmanbarryp hematopoieticstemcelldifferentiationregulatedbyasingleubiquitinligasesubstratecomplex
AT palomeroteresa hematopoieticstemcelldifferentiationregulatedbyasingleubiquitinligasesubstratecomplex
AT ferrandoadolfo hematopoieticstemcelldifferentiationregulatedbyasingleubiquitinligasesubstratecomplex
AT aifantisiannis hematopoieticstemcelldifferentiationregulatedbyasingleubiquitinligasesubstratecomplex