The monosaccharide addition of an N-acetylglucosamine to serine and threonine residues of nuclear and cytosolic proteins (O-GlcNAc) is a posttranslational modification emerging as a general regulator of many cellular processes, including signal transduction, cell division, and transcription. The sole mouse O-GlcNAc transferase (OGT) is essential for embryonic development. To understand the role of OGT in mouse development better, we mapped sites of O-GlcNAcylation of nuclear proteins in mouse embryonic stem cells (ESCs). Here, we unambiguously identify over 60 nuclear proteins as O-GlcNAcylated, several of which are crucial for mouse ESC cell maintenance. Furthermore, we extend the connection between OGT and Polycomb group genes from flies to mammals, showing Polycomb repressive complex 2 is necessary to maintain normal levels of OGT and for the correct cellular distribution of O-GlcNAc. Together, these results provide insight into how OGT may regulate transcription in early development, possibly by modifying proteins important to maintain the ESC transcriptional repertoire.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111310 | PMC |
| http://dx.doi.org/10.1073/pnas.1019289108 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Insights Into the Role of Bmi-1 Deregulation in Promoting Stemness and Therapy Resistance in Glioblastoma: A Narrative Review.
Cancer Med
January 2025
Faculty of Medical Sciences, Neuroscience Research Center, Lebanese University, Hadath, Lebanon.
Background: Glioblastoma (GBM) is the most common primary brain tumor in adults and has a median survival of less than 15 months. Advancements in the field of epigenetics have expanded our understanding of cancer biology and helped explain the molecular heterogeneity of these tumors. B-cell-specific Moloney murine leukemia virus insertion site-1 (Bmi-1) is a member of the highly conserved polycomb group (PcG) protein family that acts as a transcriptional repressor of multiple genes, including those that determine cell proliferation and differentiation.
View Article and Find Full Text PDFGenetic and epigenetic characterization of sarcoma stem cells across subtypes identifies EZH2 as a therapeutic target.
NPJ Precis Oncol
January 2025
Department of Orthopedic Surgery, University of California Davis, Sacramento, CA, 95817, USA.
High-grade soft tissue sarcomas (STS) are a heterogeneous and aggressive set of cancers. Failure to respond anthracycline chemotherapy, standard first-line treatment, is associated with poor outcomes. We investigated the contribution of STS cancer stem cells (STS-CSCs) to doxorubicin resistance.
View Article and Find Full Text PDFExploring oncogenic roles and clinical significance of EZH2: focus on non-canonical activities.
Ther Adv Med Oncol
January 2025
Department of Molecular Biology of Cancer, Medical University of Lodz, Mazowiecka 6/8, Lodz 92-215, Poland.
The enhancer of zeste homolog 2 (EZH2) is a catalytic component of Polycomb repressive complex 2 (PRC2) mediating the methylation of histone 3 lysine 27 (H3K27me3) and hence the epigenetic repression of target genes, known as canonical function. Growing evidence indicates that EZH2 has non-canonical roles that are exerted as PRC2-dependent and PRC2-independent methylation of non-histone proteins, and methyltransferase-independent interactions of EZH2 with various proteins contributing to gene expression regulation and alterations in the protein stability. is frequently mutated and/or its expression is deregulated in various cancer types.
View Article and Find Full Text PDFStructural basis for the inhibition of PRC2 by active transcription histone posttranslational modifications.
Nat Struct Mol Biol
January 2025
Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Polycomb repressive complex 2 (PRC2) trimethylates histone H3 on K27 (H3K27me3) leading to gene silencing that is essential for embryonic development and maintenance of cell identity. PRC2 is regulated by protein cofactors and their crosstalk with histone modifications. Trimethylated histone H3 on K4 (H3K4me3) and K36 (H3K36me3) localize to sites of active transcription and inhibit PRC2 activity through unknown mechanisms.
View Article and Find Full Text PDFEZH2 modulates mRNA splicing and exerts part of its oncogenic function through repression of splicing factors in CML.
Leukemia
January 2025
Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
The polycomb protein EZH2 is up-regulated in Chronic Myeloid Leukaemia (CML) and associated with transcriptional reprogramming. Here we tested whether EZH2 might also act as a modulator of the mRNA splicing landscape to elicit its oncogenic function in CML. We treated CML cell lines with EZH2 inhibitors and detected differential splicing of several hundreds of events, potentially caused by the transcriptional regulation of splicing factors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!