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

Publication date: Available online 10 February 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): L. Fouani, M.L.H. Huang, L. Cole, P.J. Jansson, Z. Kovacevic, D.R. RichardsonAbstractMicrotubules 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 associa...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research