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Article
Recruitment of FBXO22 for targeted degradation of NSD2
Targeted protein degradation (TPD) is an emerging therapeutic strategy that would benefit from new chemical entities with which to recruit a wider variety of ubiquitin E3 ligases to target proteins for proteas...
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Article
Open AccessPRMT inhibition induces a viral mimicry response in triple-negative breast cancer
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and few effective therapies. Here we identified MS023, an inhibitor of type I protein arginine methylt...
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Article
Open AccessGLUT1 inhibition blocks growth of RB1-positive triple negative breast cancer
Triple negative breast cancer (TNBC) is a deadly form of breast cancer due to the development of resistance to chemotherapy affecting over 30% of patients. New therapeutics and companion biomarkers are urgentl...
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Article
Open AccessA chemical toolbox for the study of bromodomains and epigenetic signaling
Bromodomains (BRDs) are conserved protein interaction modules which recognize (read) acetyl-lysine modifications, however their role(s) in regulating cellular states and their potential as targets for the deve...
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Article
Open AccessTargeting bivalency de-represses Indian Hedgehog and inhibits self-renewal of colorectal cancer-initiating cells
In embryonic stem cells, promoters of key lineage-specific differentiation genes are found in a bivalent state, having both activating H3K4me3 and repressive H3K27me3 histone marks, making them poised for tran...
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Article
Discovery of a chemical probe for the L3MBTL3 methyllysine reader domain
Methylation of lysine residues regulates chromatin function in part by recruiting readers to these marks. UNC1215, a selective antagonist of the methyllysine reader L3MBTL3 with a polyvalent mode of interactio...
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Article
Molecular basis of Pirh2-mediated p53 ubiquitylation
Pirh2 is one of several ubiquitin ligases known to modify and negatively regulate p53. Solution studies reveal the structures of the three Pirh2 domains and indicate that the C-terminal domain of Pirh2 interac...
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Article
Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1
DNA methylation is a key epigenetic process and the faithful maintenance of DNA methylation patterns is essential to the wellbeing of mammalian cells. This means that cells need a mechanism to identify the par...
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Article
Molecular recognition of p53 and MDM2 by USP7/HAUSP
The ubiquitin-specific protease, USP7, has key roles in the p53 pathway whereby it stabilizes both p53 and MDM2. We show that the N-terminal domain of USP7 binds two closely spaced 4-residue sites in both p53 ...
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Article
Characterization of a family of vacuolar Na+/H+ antiporters in Arabidopsis thaliana
A family of AtNHX1-like genes of Arabidopsis thaliana, coding for vacuolar Na+/H+ antiporters, was cloned and functionally characterized by their heterologous expression in yeast mutants lacking an endosomal vacu...
