MAP3K4 Controls the Chromatin Modifier HDAC6 During Trophoblast Stem Cell Epithelial-to-Mesenchymal Transition

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2017 Mar 9

PMID 28273454

Citations 29

Authors

Robert J Mobley

Deepthi Raghu

Lauren D Duke

Kayley Abell-Hart

Jon S Zawistowski

Kyla Lutz

Shawn M Gomez

Sujoy Roy

Ramin Homayouni

Gary L Johnson

Amy N Abell

Affiliations

Soon will be listed here.

Abstract

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 (TS 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 TS 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 TS 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.

Citing Articles

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