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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
2010
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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 |
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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 |
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