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Negative Regulation of Erythroid Differentiation via the CBX8-TRIM28 Axis

Although the mechanism of chronic myeloid leukemia (CML) initiation through BCR/ABL oncogene has been well characterized, CML cell differentiation into erythroid lineage cells remains poorly understood. Using CRISPR-Cas9 screening, we identify Chromobox 8 (CBX8) as a negative regulator of K562 cell...

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Autores principales: Kim, Hyun Jeong, Park, Jin Woo, Kang, Joo-Young, Seo, Sang-Beom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Molecular and Cellular Biology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8334346/
https://www.ncbi.nlm.nih.gov/pubmed/34253692
http://dx.doi.org/10.14348/molcells.2021.0012
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author Kim, Hyun Jeong
Park, Jin Woo
Kang, Joo-Young
Seo, Sang-Beom
author_facet Kim, Hyun Jeong
Park, Jin Woo
Kang, Joo-Young
Seo, Sang-Beom
author_sort Kim, Hyun Jeong
collection PubMed
description Although the mechanism of chronic myeloid leukemia (CML) initiation through BCR/ABL oncogene has been well characterized, CML cell differentiation into erythroid lineage cells remains poorly understood. Using CRISPR-Cas9 screening, we identify Chromobox 8 (CBX8) as a negative regulator of K562 cell differentiation into erythrocytes. CBX8 is degraded via proteasomal pathway during K562 cell differentiation, which activates the expression of erythroid differentiation-related genes that are repressed by CBX8 in the complex of PRC1. During the differentiation process, the serine/threonine-protein kinase PIM1 phosphorylates serine 196 on CBX8, which contributes to CBX8 reduction. When CD235A expression levels are analyzed, the result reveals that the knockdown of PIM1 inhibits K562 cell differentiation. We also identify TRIM28 as another interaction partner of CBX8 by proteomic analysis. Intriguingly, TRIM28 maintains protein stability of CBX8 and TRIM28 loss significantly induces proteasomal degradation of CBX8, resulting in an acceleration of erythroid differentiation. Here, we demonstrate the involvement of the CBX8-TRIM28 axis during CML cell differentiation, suggesting that CBX8 and TRIM28 are promising novel targets for CML research.
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spelling pubmed-83343462021-08-11 Negative Regulation of Erythroid Differentiation via the CBX8-TRIM28 Axis Kim, Hyun Jeong Park, Jin Woo Kang, Joo-Young Seo, Sang-Beom Mol Cells Research Article Although the mechanism of chronic myeloid leukemia (CML) initiation through BCR/ABL oncogene has been well characterized, CML cell differentiation into erythroid lineage cells remains poorly understood. Using CRISPR-Cas9 screening, we identify Chromobox 8 (CBX8) as a negative regulator of K562 cell differentiation into erythrocytes. CBX8 is degraded via proteasomal pathway during K562 cell differentiation, which activates the expression of erythroid differentiation-related genes that are repressed by CBX8 in the complex of PRC1. During the differentiation process, the serine/threonine-protein kinase PIM1 phosphorylates serine 196 on CBX8, which contributes to CBX8 reduction. When CD235A expression levels are analyzed, the result reveals that the knockdown of PIM1 inhibits K562 cell differentiation. We also identify TRIM28 as another interaction partner of CBX8 by proteomic analysis. Intriguingly, TRIM28 maintains protein stability of CBX8 and TRIM28 loss significantly induces proteasomal degradation of CBX8, resulting in an acceleration of erythroid differentiation. Here, we demonstrate the involvement of the CBX8-TRIM28 axis during CML cell differentiation, suggesting that CBX8 and TRIM28 are promising novel targets for CML research. Korean Society for Molecular and Cellular Biology 2021-07-31 2021-07-13 /pmc/articles/PMC8334346/ /pubmed/34253692 http://dx.doi.org/10.14348/molcells.2021.0012 Text en © The Korean Society for Molecular and Cellular Biology. All rights reserved. https://creativecommons.org/licenses/by-nc-sa/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ (https://creativecommons.org/licenses/by-nc-sa/3.0/)
spellingShingle Research Article
Kim, Hyun Jeong
Park, Jin Woo
Kang, Joo-Young
Seo, Sang-Beom
Negative Regulation of Erythroid Differentiation via the CBX8-TRIM28 Axis
title Negative Regulation of Erythroid Differentiation via the CBX8-TRIM28 Axis
title_full Negative Regulation of Erythroid Differentiation via the CBX8-TRIM28 Axis
title_fullStr Negative Regulation of Erythroid Differentiation via the CBX8-TRIM28 Axis
title_full_unstemmed Negative Regulation of Erythroid Differentiation via the CBX8-TRIM28 Axis
title_short Negative Regulation of Erythroid Differentiation via the CBX8-TRIM28 Axis
title_sort negative regulation of erythroid differentiation via the cbx8-trim28 axis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8334346/
https://www.ncbi.nlm.nih.gov/pubmed/34253692
http://dx.doi.org/10.14348/molcells.2021.0012
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