PHRF1 promotes migration and invasion by modulating ZEB1 expression
Journal
PLoS ONE
Journal Volume
15
Journal Issue
07-Jul
Date Issued
2020
Author(s)
Abstract
PHRF1 (PHD and RING finger domain-containing protein 1) suppresses acute promyelocytic leukemia (APL) by promoting TGIF (TG-interacting factor) ubiquitination, while the PMLRARα protein interferes with PHRF1-mediated TGIF breakdown to facilitate APL. Beyond its role in APL tumorigenesis, PHRF1 contributes to non-homologous end-joining by linking H3K36 methylation and Nbs1 upon DNA damage insults. However, little is known regarding its function in tumor invasion. Here we highlight the unreported details of PHRF1 in the invasion of lung cancer cells by modulating the transcriptional level of ZEB1, a prominent regulator involved in epithelial-mesenchymal transition. PHRF1 associated with the phosphorylated C-terminal repeat domain of Rpb1, the large subunit of RNA polymerase II, through its C-terminal Set2 Rpb1 Interacting (SRI) domain. Chromatin immunoprecipitation revealed that PHRF1 bound to the proximal region adjacent to the transcription start site of ZEB1. SRI-deleted PHRF1 neither associated with Rpb1 nor increased ZEB1's expression. Collectively, PHRF1 might take the stage at migration and invasion by modulating the expression of ZEB1. Copyright: ? 2020 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
SDGs
Other Subjects
plant homeodomain and ring domain containing protein 1; RNA polymerase II; RNA polymerase II Rpb1; transcription factor ZEB1; tumor suppressor protein; unclassified drug; membrane protein; PHD and RING finger domain-containing protein 1, human; transcription factor ZEB1; tumor marker; ZEB1 protein, human; animal cell; animal experiment; animal model; animal tissue; Article; cancer cell; carboxy terminal sequence; carboxy terminal sequence Set2 Rpb1 interacting domain; cell migration; chromatin immunoprecipitation; controlled study; epithelial mesenchymal transition; gene expression; genetic transcription; human; human cell; lung cancer; nonhuman; protein binding; protein depletion; protein domain; protein function; protein phosphorylation; protein protein interaction; regulator gene; transcription initiation; tumor invasion; ZEB1 gene; animal; apoptosis; cell motion; cell proliferation; drug screening; gene expression regulation; genetics; lung tumor; metabolism; mouse; pathology; prognosis; tumor cell culture; tumor invasion; Animals; Apoptosis; Biomarkers, Tumor; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Membrane Proteins; Mice; Neoplasm Invasiveness; Prognosis; Tumor Cells, Cultured; Xenograft Model Antitumor Assays; Zinc Finger E-box-Binding Homeobox 1
Type
journal article