TY - JOUR
T1 - Regulation of ZEB1 Function and Molecular Associations in Tumor Progression and Metastasis
AU - Perez-Oquendo, Mabel
AU - Gibbons, Don L.
N1 - Funding Information:
Work in the lab is supported by CPRIT-MIRA RP160652-P3, and NCI R37CA214609. M.P.-O. is supported by the Ruth L. Kirschstein National Research Service Award Individual Predoctoral Fellowship to Promote Diversity in Health-Related Research (NIH NCI F31CA268343).
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - Zinc finger E-box binding homeobox 1 (ZEB1) is a pleiotropic transcription factor frequently expressed in carcinomas. ZEB1 orchestrates the transcription of genes in the control of several key developmental processes and tumor metastasis via the epithelial-to-mesenchymal transition (EMT). The biological function of ZEB1 is regulated through pathways that influence its transcription and post-transcriptional mechanisms. Diverse signaling pathways converge to induce ZEB1 activity; however, only a few studies have focused on the molecular associations or functional changes of ZEB1 by post-translational modifications (PTMs). Due to the robust effect of ZEB1 as a transcription repressor of epithelial genes during EMT, the contribution of PTMs in the regulation of ZEB1-targeted gene expression is an active area of investigation. Herein, we review the pivotal roles that phosphorylation, acetylation, ubiquitination, sumoylation, and other modifications have in regulating the molecular associations and behavior of ZEB1. We also outline several questions regarding the PTM-mediated regulation of ZEB1 that remain unanswered. The areas of research covered in this review are contributing to new treatment strategies for cancer by improving our mechanistic understanding of ZEB1-mediated EMT.
AB - Zinc finger E-box binding homeobox 1 (ZEB1) is a pleiotropic transcription factor frequently expressed in carcinomas. ZEB1 orchestrates the transcription of genes in the control of several key developmental processes and tumor metastasis via the epithelial-to-mesenchymal transition (EMT). The biological function of ZEB1 is regulated through pathways that influence its transcription and post-transcriptional mechanisms. Diverse signaling pathways converge to induce ZEB1 activity; however, only a few studies have focused on the molecular associations or functional changes of ZEB1 by post-translational modifications (PTMs). Due to the robust effect of ZEB1 as a transcription repressor of epithelial genes during EMT, the contribution of PTMs in the regulation of ZEB1-targeted gene expression is an active area of investigation. Herein, we review the pivotal roles that phosphorylation, acetylation, ubiquitination, sumoylation, and other modifications have in regulating the molecular associations and behavior of ZEB1. We also outline several questions regarding the PTM-mediated regulation of ZEB1 that remain unanswered. The areas of research covered in this review are contributing to new treatment strategies for cancer by improving our mechanistic understanding of ZEB1-mediated EMT.
KW - epigenetic
KW - epithelial-to-mesenchymal transition (EMT)
KW - metastasis
KW - post-translational modifications
KW - transcription factor
KW - ZEB1
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U2 - 10.3390/cancers14081864
DO - 10.3390/cancers14081864
M3 - Review article
C2 - 35454770
AN - SCOPUS:85127760704
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 8
M1 - 1864
ER -