During mitosis ZEB1 "switches" from being a chromatin-bound epithelial gene repressor, to become a microtubule-associated protein.

Fouani, L; Huang, MLH; Cole, L; Jansson, PJ; Kovacevic, Z; Richardson, DR

During mitosis ZEB1 "switches" from being a chromatin-bound epithelial gene repressor, to become a microtubule-associated protein.

Fouani, L Huang, MLH Cole, L

Jansson, PJ Kovacevic, Z Richardson, DR

Permalink

Publisher:: Elsevier BV
Publication Type:: Journal Article
Citation:: Biochimica et biophysica acta. Molecular cell research, 2020, 1867, (7), pp. 118673
Issue Date:: 2020-07

Closed Access

	Filename	Description	Size
	main.pdf	Accepted version	12.27 MB	Adobe PDF	View/Open

Copyright Clearance Process

Recently Added
In Progress
Closed Access

This item is closed access and not available.

Full metadata record

Field	Value	Language
dc.contributor.author	Fouani, L
dc.contributor.author	Huang, MLH
dc.contributor.author	Cole, L https://orcid.org/0000-0001-9206-9272
dc.contributor.author	Jansson, PJ
dc.contributor.author	Kovacevic, Z
dc.contributor.author	Richardson, DR
dc.date.accessioned	2020-08-13T06:47:03Z
dc.date.available	2020-02-02
dc.date.available	2020-08-13T06:47:03Z
dc.date.issued	2020-07
dc.identifier.citation	Biochimica et biophysica acta. Molecular cell research, 2020, 1867, (7), pp. 118673
dc.identifier.issn	0167-4889
dc.identifier.issn	1879-2596
dc.identifier.uri	http://hdl.handle.net/10453/142103
dc.description.abstract	Microtubules are polymers of α/β-tubulin, with microtubule organization being regulated by microtubule-associated proteins (MAPs). Herein, we describe a novel role for the epithelial gene repressor, zinc finger E-box-binding homeobox 1 (ZEB1), that "switches" from a chromatin-associated protein during interphase, to a MAP that associates with α-, β- and γ-tubulin during mitosis. Additionally, ZEB1 was also demonstrated to associate with γ-tubulin at the microtubule organizing center (MTOC). Using confocal microscopy, ZEB1 localization was predominantly nuclear during interphase, with α/β-tubulin being primarily cytoplasmic and the association between these proteins being minimal. However, during the stages of mitosis, ZEB1 co-localization with α-, β-, and γ-tubulin was significantly increased, with the association commonly peaking during metaphase in multiple tumor cell-types. ZEB1 was also observed to accumulate in the cleavage furrow during cytokinesis. The increased interaction between ZEB1 and α-tubulin during mitosis was also confirmed using the proximity ligation assay. In contrast to ZEB1, its paralog ZEB2, was mainly perinuclear and cytoplasmic during interphase, showing some co-localization with α-tubulin during mitosis. Considering the association between ZEB1 with α/β/γ-tubulin during mitosis, studies investigated ZEB1's role in the cell cycle. Silencing ZEB1 resulted in a G2-M arrest, which could be mediated by the up-regulation of p21Waf1/Cip1 and p27Kip1 that are known downstream targets repressed by ZEB1. However, it cannot be excluded the G2/M arrest observed after ZEB1 silencing is not due to its roles as a MAP. Collectively, ZEB1 plays a role as a MAP during mitosis and could be functionally involved in this process.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Elsevier BV
dc.relation.ispartof	Biochimica et biophysica acta. Molecular cell research
dc.relation.isbasedon	10.1016/j.bbamcr.2020.118673
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	0601 Biochemistry and Cell Biology, 1108 Medical Microbiology
dc.subject.classification	Biochemistry & Molecular Biology
dc.title	During mitosis ZEB1 "switches" from being a chromatin-bound epithelial gene repressor, to become a microtubule-associated protein.
dc.type	Journal Article
utslib.citation.volume	1867
utslib.location.activity	Netherlands
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	1108 Medical Microbiology
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	closed_access	*
dc.date.updated	2020-08-13T06:45:52Z
pubs.issue	7
pubs.publication-status	Published
pubs.volume	1867
utslib.citation.issue	7

Abstract:

Microtubules are polymers of α/β-tubulin, with microtubule organization being regulated by microtubule-associated proteins (MAPs). Herein, we describe a novel role for the epithelial gene repressor, zinc finger E-box-binding homeobox 1 (ZEB1), that "switches" from a chromatin-associated protein during interphase, to a MAP that associates with α-, β- and γ-tubulin during mitosis. Additionally, ZEB1 was also demonstrated to associate with γ-tubulin at the microtubule organizing center (MTOC). Using confocal microscopy, ZEB1 localization was predominantly nuclear during interphase, with α/β-tubulin being primarily cytoplasmic and the association between these proteins being minimal. However, during the stages of mitosis, ZEB1 co-localization with α-, β-, and γ-tubulin was significantly increased, with the association commonly peaking during metaphase in multiple tumor cell-types. ZEB1 was also observed to accumulate in the cleavage furrow during cytokinesis. The increased interaction between ZEB1 and α-tubulin during mitosis was also confirmed using the proximity ligation assay. In contrast to ZEB1, its paralog ZEB2, was mainly perinuclear and cytoplasmic during interphase, showing some co-localization with α-tubulin during mitosis. Considering the association between ZEB1 with α/β/γ-tubulin during mitosis, studies investigated ZEB1's role in the cell cycle. Silencing ZEB1 resulted in a G2-M arrest, which could be mediated by the up-regulation of p21Waf1/Cip1 and p27Kip1 that are known downstream targets repressed by ZEB1. However, it cannot be excluded the G2/M arrest observed after ZEB1 silencing is not due to its roles as a MAP. Collectively, ZEB1 plays a role as a MAP during mitosis and could be functionally involved in this process.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/142103