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Jan 7, 2025 | 00012-2/fulltext&sz=64)
jbc.org | Kathleen M. Mulvaney |William Sellers |Eric S. Fischer
IntroductionArginine methylation is a post-translational modification that results in the addition of one or two methyl groups to the guanidino moiety of arginine from the cofactor S-Adenosyl-L-Methionine (SAM) (1-3). Among the three types of protein arginine methyltransferases (PRMTs), type II PRMTs are responsible for installing symmetric dimethyl-arginine (SDMA) marks (4, 5). Type II PRMTs include PRMT5 and PRMT9, where PRMT5 is the main writer of cellular SDMA (6).
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Jul 28, 2024 | 
nature.com | Moritz Hunkeler |Mingxing Teng |Justine C. Rutter |Anna M Schmoker |Rebecca Metivier |Woong Sub Byun | +9 more
AbstractMolecular glues are proximity-inducing small molecules that have emerged as an attractive therapeutic approach. However, developing molecular glues remains challenging, requiring innovative mechanistic strategies to stabilize neoprotein interfaces and expedite discovery. Here we unveil a trans-labeling covalent molecular glue mechanism, termed ‘template-assisted covalent modification’.
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Jun 18, 2024 | 
nature.com | Han-Yuan Liu |Theresia Reindl |Ryan Golden |Katherine A. Donovan |Eric S. Fischer |Nathanael S. Gray
AbstractViral genetic diversity presents significant challenges in developing antivirals with broad-spectrum activity and high barriers to resistance. Here we report development of proteolysis targeting chimeras (PROTACs) targeting the dengue virus envelope (E) protein through coupling of known E fusion inhibitors to ligands of the CRL4CRBN E3 ubiquitin ligase.
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Apr 29, 2024 | 
nature.com | Raymond Carter |Baranda S. Hansen |Katherine A. Donovan |Moritz Hunkeler |Wojciech Rosikiewicz |Meghan G. McReynolds | +8 more
Correction to: Nature https://doi.org/10.1038/s41586-024-07250-1 Published online 27 March 2024In the version of the article initially published, the far-right labels in Fig. 4h (now reading “Viable cells” and “Lethal in SMARCB1-deficient RT cells”) were swapped and have now been corrected in the HTML and PDF versions of the article. About this articleRadko-Juettner, S., Yue, H., Myers, J.A. et al. Author Correction: Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNF.
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Mar 27, 2024 | 
nature.com | Raymond Carter |Baranda S. Hansen |Katherine A. Donovan |Moritz Hunkeler |Wojciech Rosikiewicz |Nada Mageed | +8 more
AbstractWhereas oncogenes can potentially be inhibited with small molecules, the loss of tumour suppressors is more common and is problematic because the tumour-suppressor proteins are no longer present to be targeted. Notable examples include SMARCB1-mutant cancers, which are highly lethal malignancies driven by the inactivation of a subunit of SWI/SNF (also known as BAF) chromatin-remodelling complexes.
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Mar 20, 2024 | 
nature.com | Hai-Tsang Huang |Ryan Lumpkin |Yuan Xiong |James Chen |Katherine A. Donovan |Eric S. Fischer | +2 more
AbstractProtein ubiquitylation controls diverse processes within eukaryotic cells, including protein degradation, and is often dysregulated in disease. Moreover, small-molecule degraders that redirect ubiquitylation activities toward disease targets are an emerging and promising therapeutic class. Over 600 E3 ubiquitin ligases are expressed in humans, but their substrates remain largely elusive, necessitating the development of new methods for their discovery.
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Feb 27, 2024 | 
science.org | Emily Erickson |Hao Cai |Leslie K. Ferrarelli |Inchul You |Grace Perry |Aurelien Dugourd | +11 more
Research ResourceCANCEREmily C. Erickson https://orcid.org/0000-0003-3494-2605, Inchul You, [...] , Grace Perry https://orcid.org/0000-0002-0404-9237, Aurelien Dugourd https://orcid.org/0000-0002-0714-028X, [...] , Katherine A. Donovan https://orcid.org/0000-0002-8539-5106, Claire Crafter https://orcid.org/0000-0001-6566-0868, Jeffrey W. Johannes https://orcid.org/0000-0001-7242-6682, Stuart Williamson https://orcid.org/0000-0002-5209-4796, Jennifer I.
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Feb 27, 2024 | science.org | Emily Erickson |Hao Cai |Leslie K. Ferrarelli |Inchul You |Grace Perry |Aurelien Dugourd | +11 more
Research ResourceCANCEREmily C. Erickson https://orcid.org/0000-0003-3494-2605, Inchul You, [...] , Grace Perry https://orcid.org/0000-0002-0404-9237, Aurelien Dugourd https://orcid.org/0000-0002-0714-028X, [...] , Katherine A. Donovan https://orcid.org/0000-0002-8539-5106, Claire Crafter https://orcid.org/0000-0001-6566-0868, Jeffrey W. Johannes https://orcid.org/0000-0001-7242-6682, Stuart Williamson https://orcid.org/0000-0002-5209-4796, Jennifer I.
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Sep 7, 2023 | 
nature.com | Zuzanna Kozicka |Katherine A. Donovan |Marko Cigler |Jonathan L. Schmid-Burgk |Daniel Häussinger |Georg E. Winter | +4 more
AbstractMolecular glue degraders are an effective therapeutic modality, but their design principles are not well understood. Recently, several unexpectedly diverse compounds were reported to deplete cyclin K by linking CDK12–cyclin K to the DDB1–CUL4–RBX1 E3 ligase.
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Mar 15, 2023 | 
nature.com | Daniela V. Wenge |Homa Rahnamoun |Richard Stone |Wenbin Xiao |Holly A. Gamlen |Aaron J. Stonestrom | +6 more
AbstractChromatin-binding proteins are critical regulators of cell state in haematopoiesis1,2. Acute leukaemias driven by rearrangement of the mixed lineage leukaemia 1 gene (KMT2Ar) or mutation of the nucleophosmin gene (NPM1) require the chromatin adapter protein menin, encoded by the MEN1 gene, to sustain aberrant leukaemogenic gene expression programs3,4,5.
