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O-GlcNAc modification regulates MTA1 transcriptional activity during breast cancer cell genotoxic adaptation.
- Source :
-
BBA - General Subjects . Aug2021, Vol. 1865 Issue 8, pN.PAG-N.PAG. 1p. - Publication Year :
- 2021
-
Abstract
- Chromatin modifier metastasis-associated protein 1 (MTA1), closely associated with tumor angiogenesis in breast cancer, plays an important role in gene expression and cancer cell behavior. Recently, an association between O-GlcNAc transferase (OGT) and MTA1 was identified by mass spectroscopy. However, the potential relationship between MTA1 and O-GlcNAc modification has not yet explored. In the current study, the role of MTA1 and its O-GlcNAc modification in breast cancer cell genotoxic adaptation was investigated through quantitative proteomics, chromatin immunoprecipitation followed by sequencing (ChIP-seq), transcriptome analysis, and loss- and gain-of-function experiments. We demonstrate that the O-GlcNAc modification promotes MTA1 to interaction with chromatin and thus changes the expression of target genes, contributing to breast cancer cell genotoxic adaptation. MTA1 is modified with O-GlcNAc residues at serine (S) residues S237/S241/S246 in adriamycin-adaptive breast cancer cells, and this modification improves the genome-wide interactions of MTA1 with gene promotor regions by enhancing its association with nucleosome remodeling and histone deacetylation (NuRD) complex. Further, O-GlcNAc modification modulates MTA1 chromatin binding, influencing the specific transcriptional regulation of genes involved in the adaptation of breast cancer cells to genotoxic stress. Our findings reveal a previously unrecognized role for O-GlcNAc-modified MTA1 in transcriptional regulation and suggest that the O-GlcNAc modification is a key to the molecular regulation of chemoresistance in breast cancers. • OGT interacts with MTA1 in breast cancer cells and promotes MTA1 O-GlcNAc modification at serine residues S237/S241/S246. • O-GlcNAc modification enhances the interaction between MTA1 and other NuRD components. • O-GlcNAc modification of MTA1 affect downstream genes expression and protect breast cancer cells against genotoxicity. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03044165
- Volume :
- 1865
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- BBA - General Subjects
- Publication Type :
- Academic Journal
- Accession number :
- 150769833
- Full Text :
- https://doi.org/10.1016/j.bbagen.2021.129930