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Article
Author Correction: The Cyclophilin A–CD147 complex promotes the proliferation and homing of multiple myeloma cells
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Article
1H, 13C and 15N backbone and sidechain assignment of the Burkholderia mallei acyl carrier protein
Acyl carrier proteins (ACPs) are universally conserved proteins amongst different species and are involved in fatty acid synthesis. Bacteria utilize ACPs as acyl carriers and donors for the synthesis of produc...
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Article
Open AccessEpitope editing enables targeted immunotherapy of acute myeloid leukaemia
Despite the considerable efficacy observed when targeting a dispensable lineage antigen, such as CD19 in B cell acute lymphoblastic leukaemia1,2, the broader applicability of adoptive immunotherapies is hampered ...
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Article
Open AccessAccelerating inhibitor discovery for deubiquitinating enzymes
Deubiquitinating enzymes (DUBs) are an emerging drug target class of ~100 proteases that cleave ubiquitin from protein substrates to regulate many cellular processes. A lack of selective chemical probes impede...
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Article
Sulfopin is a covalent inhibitor of Pin1 that blocks Myc-driven tumors in vivo
The peptidyl-prolyl isomerase, Pin1, is exploited in cancer to activate oncogenes and inactivate tumor suppressors. However, despite considerable efforts, Pin1 has remained an elusive drug target. Here, we scr...
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Article
Open AccessBRCA1 binds TERRA RNA and suppresses R-Loop-based telomeric DNA damage
R-loop structures act as modulators of physiological processes such as transcription termination, gene regulation, and DNA repair. However, they can cause transcription-replication conflicts and give rise to g...
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Article
Identification of a potent and selective covalent Pin1 inhibitor
Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is commonly overexpressed in human cancers, including pancreatic ductal adenocarcinoma (PDAC). While Pin1 is dispensable for viability in mice, it is ...
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Article
Glucose-dependent partitioning of arginine to the urea cycle protects β-cells from inflammation
Chronic inflammation is linked to diverse disease processes, but the intrinsic mechanisms that determine cellular sensitivity to inflammation are incompletely understood. Here, we show the contribution of gluc...
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Article
Open AccessSelective USP7 inhibition elicits cancer cell killing through a p53-dependent mechanism
Ubiquitin specific peptidase 7 (USP7) is a deubiquitinating enzyme (DUB) that removes ubiquitin tags from specific protein substrates in order to alter their degradation rate and sub-cellular localization. USP...
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Article
Development of a covalent inhibitor of gut bacterial bile salt hydrolases
Bile salt hydrolase (BSH) enzymes are widely expressed by human gut bacteria and catalyze the gateway reaction leading to secondary bile acid formation. Bile acids regulate key metabolic and immune processes b...
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Article
Architecture of autoinhibited and active BRAF–MEK1–14-3-3 complexes
RAF family kinases are RAS-activated switches that initiate signalling through the MAP kinase cascade to control cellular proliferation, differentiation and survival1–3. RAF activity is tightly regulated and inap...
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Article
Differential contribution of the mitochondrial translation pathway to the survival of diffuse large B-cell lymphoma subsets
Diffuse large B-cell lymphomas (DLBCLs) are a highly heterogeneous group of tumors in which subsets share molecular features revealed by gene expression profiles and metabolic fingerprints. While B-cell recept...
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Article
Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors
A small molecule inhibits CDK12 and CDK13 activity through covalent modification of Cys residues and reveals a role of the two kinases in regulating Pol II processivity and super-enhancer-driven transcription ...
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Article
Structure and mechanism of activity-based inhibition of the EGF receptor by Mig6
Mig6 phosphorylation at two consecutive tyrosines induces rearrangements that lead to Mig6 sticking to and inhibiting the same EGFR that catalyzed its phosphorylation. This mechanism may serve as a basis for i...
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Article
The Cyclophilin A–CD147 complex promotes the proliferation and homing of multiple myeloma cells
Cyclophilin A, secreted by bone marrow endothelial cells, acts as a chemotactic factor for myeloma cells, which helps explain their homing to the bone marrow and suggests a potential new therapeutic strategy.
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Article
Pharmacological targeting of the pseudokinase Her3
The use of ATP competitive kinase inhibitors against the pseudokinase Her3 has been largely unsuccessful. Hydrophobic tagging of a covalent kinase inhibitor promotes Her3 degradation and prevents productive di...
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Article
Targeting transcription regulation in cancer with a covalent CDK7 inhibitor
Here, a covalent inhibitor targeting cyclin-dependent kinase 7 (CDK7) demonstrates in vitro and in vivo efficacy against T-cell acute lymphoblastic leukaemia by downregulating oncogenic transcriptional programs.
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Article
Protected Amine Labels: A Versatile Molecular Scaffold for Multiplexed Nominal Mass and Sub-Da Isotopologue Quantitative Proteomic Reagents
We assemble a versatile molecular scaffold from simple building blocks to create binary and multiplexed stable isotope reagents for quantitative mass spectrometry. Termed Protected Amine Labels (PAL), these re...
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Article
Structure of a pseudokinase-domain switch that controls oncogenic activation of Jak kinases
Equivalent mutations in the pseudokinase domain of Jak2 (V617F) and Jak1 (V658F) result in myeloproliferative disorders. Crystal structures of wild-type and the V658F mutant of human Jak1 spanning the pseudoki...
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Article
Genome-scale proteome quantification by DEEP SEQ mass spectrometry
Advances in chemistry and massively parallel detection underlie DNA-sequencing platforms that are poised for application in personalized medicine. In stark contrast, systematic generation of protein-level data...
