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

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Fouani, L
Huang, MLH
Cole, L
Jansson, PJ
Kovacevic, Z
Richardson, DR
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2020
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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.

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Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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1867

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7

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Biochemistry and cell biology

Medical microbiology

Science & Technology

Life Sciences & Biomedicine

Cell Biology

ZEB1

Molecular Biology

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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, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2020, 1867 (7), pp. 118673

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