MAP3K4 Controls the Chromatin Modifier HDAC6 during Trophoblast Stem Cell Epithelial-to-Mesenchymal Transition
Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved..
The first epithelial-to-mesenchymal transition (EMT) occurs in trophoblast stem (TS) cells during implantation. Inactivation of the serine/threonine kinase MAP3K4 in TS cells (TSKI4 cells) induces an intermediate state of EMT, where cells retain stemness, lose epithelial markers, and gain mesenchymal characteristics. Investigation of relationships among MAP3K4 activity, stemness, and EMT in TS cells may reveal key regulators of EMT. Here, we show that MAP3K4 activity controls EMT through the ubiquitination and degradation of HDAC6. Loss of MAP3K4 activity in TSKI4 cells results in elevated HDAC6 expression and the deacetylation of cytoplasmic and nuclear targets. In the nucleus, HDAC6 deacetylates the promoters of tight junction genes, promoting the dissolution of tight junctions. Importantly, HDAC6 knockdown in TSKI4 cells restores epithelial features, including cell-cell adhesion and barrier formation. These data define a role for HDAC6 in regulating gene expression during transitions between epithelial and mesenchymal phenotypes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
Cell reports - 18(2017), 10 vom: 07. März, Seite 2387-2400 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mobley, Robert J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.11.2017 Date Revised 13.11.2018 published: Print Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2017.02.030 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM26964637X |
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| 100 | 1 | |a Mobley, Robert J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a MAP3K4 Controls the Chromatin Modifier HDAC6 during Trophoblast Stem Cell Epithelial-to-Mesenchymal Transition |
| 264 | 1 | |c 2017 | |
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| 500 | |a Date Completed 28.11.2017 | ||
| 500 | |a Date Revised 13.11.2018 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a The first epithelial-to-mesenchymal transition (EMT) occurs in trophoblast stem (TS) cells during implantation. Inactivation of the serine/threonine kinase MAP3K4 in TS cells (TSKI4 cells) induces an intermediate state of EMT, where cells retain stemness, lose epithelial markers, and gain mesenchymal characteristics. Investigation of relationships among MAP3K4 activity, stemness, and EMT in TS cells may reveal key regulators of EMT. Here, we show that MAP3K4 activity controls EMT through the ubiquitination and degradation of HDAC6. Loss of MAP3K4 activity in TSKI4 cells results in elevated HDAC6 expression and the deacetylation of cytoplasmic and nuclear targets. In the nucleus, HDAC6 deacetylates the promoters of tight junction genes, promoting the dissolution of tight junctions. Importantly, HDAC6 knockdown in TSKI4 cells restores epithelial features, including cell-cell adhesion and barrier formation. These data define a role for HDAC6 in regulating gene expression during transitions between epithelial and mesenchymal phenotypes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a HDAC6 | |
| 650 | 4 | |a MAP3K4 | |
| 650 | 4 | |a chromatin remodelers | |
| 650 | 4 | |a development | |
| 650 | 4 | |a epigenetics | |
| 650 | 4 | |a epithelial to mesenchymal transition | |
| 650 | 4 | |a histone acetylation | |
| 650 | 4 | |a histone deacetylase | |
| 650 | 4 | |a tight junctions | |
| 650 | 4 | |a trophoblast stem cells | |
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| 700 | 1 | |a Raghu, Deepthi |e verfasserin |4 aut | |
| 700 | 1 | |a Duke, Lauren D |e verfasserin |4 aut | |
| 700 | 1 | |a Abell-Hart, Kayley |e verfasserin |4 aut | |
| 700 | 1 | |a Zawistowski, Jon S |e verfasserin |4 aut | |
| 700 | 1 | |a Lutz, Kyla |e verfasserin |4 aut | |
| 700 | 1 | |a Gomez, Shawn M |e verfasserin |4 aut | |
| 700 | 1 | |a Roy, Sujoy |e verfasserin |4 aut | |
| 700 | 1 | |a Homayouni, Ramin |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Gary L |e verfasserin |4 aut | |
| 700 | 1 | |a Abell, Amy N |e verfasserin |4 aut | |
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