Chemical Ligand Space of Cereblon

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Cyclic GMP-AMP synthase (cGAS) senses aberrant DNA during infection, cancer and inflammatory disease, and initiates potent innate immune responses through the synthesis of 2 ' 3 '-cyclic GMP-AMP (cGAMP)1-7. The indiscriminate activity of cGAS towards DNA d ...

DNA damage signaling following DNA double-strand breaks (DSBs) involves numerous regulating proteins, which dynamically recognize ('read') and alter ('write' or 'erase') histone post-translational modifications (PTMs). Among these PTMs, the ubiquitin syste ...

The cellular protein levels are determined by protein synthesis and turnover rates. Two processes are involved in the proteome's turnover in proliferating cells: protein degradation and dilution. In theory, maintaining the cellular proteome concentration, ...

We present herein the design of a nano-electrospray ion source capable of reliable generation of large quantities of microsolvated ions. The source is based on a triple molecular skimmer scheme and can be quickly tuned to generate bare ions or their ionic ...

The cnidarian-dinoflagellate symbiosis is a mutualistic intracellular association based on the photosynthetic activity of the endosymbiont. This relationship involves significant constraints and requires co-evolution processes, such as an extensive capacit ...

Hunter's syndrome (mucopolysaccharidosis type II) is a rare X-linked lysosomal storage disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene. Motivated by the case of a child affected by this syndrome, we compared the intracellular fate of w ...

The transcription factor STAT3 is frequently activated in human solid and hematological malignancies and remains a challenging therapeutic target with no approved drugs to date. Here, we develop synthetic antibody mimetics, termed monobodies, to interfere ...

Monobodies are small engineered binding proteins that, upon expression in cells, can inhibit signaling of cytosolic oncoproteins with outstanding selectivity. Efficacy may be further increased by inducing degradation of monobody targets through fusion to t ...

Long interspersed element-1 (LINE-1, L1) is a mobile genetic element comprising about 17% of the human genome. L1 utilizes an endonuclease to insert L1 cDNA into the target genomic DNA, which induces double-strand DNA breaks in the human genome and activat ...

Dynamic regulation of chromatin, a structure consisting of DNA and histone proteins, is mediated through histone post-translational modifications (PTMs) and effector proteins. HP1a and PRC2 are recruited to repressive PTMs (H3K9me3, H3K27me3) and enable he ...

Cells need to reliably control their proteome composition to maintain homeostasis and regulate growth. How protein synthesis and degradation interplay to control protein expression levels remains unclear. Here, we combined a tandem fluorescent timer and pu ...

Targeted cancer therapy is a very promising concept; however, small molecule inhibitors only exist for a limited number of oncoproteins and resistance development limits their clinical use. Different engineered non-antibody scaffolds are being explored to ...

RAPTA compounds, ([Ru(eta(6)-arene)(PTA)Cl-2], PTA = 1,3,5-triaza-7-phosphaadamantane), have been reported to overcome drug resistance in cisplatin resistant cells. However, the exact mechanism of these complexes is still largely unexplored. In this study, ...

Many membrane proteins fold inefficiently and require the help of enzymes and chaperones. Here we reveal a novel folding assistance system that operates on membrane proteins from the cytosolic side of the endoplasmic reticulum (ER). We show that folding of ...

Folding-defective proteins must be cleared efficiently from the endoplasmic reticulum (ER) to prevent perturbation of the folding environment and to maintain cellular proteostasis. Misfolded proteins engage dislocation machineries (dislocons) built around ...

The Drosophila humoral innate immune response fights infection by producing antimicrobial peptides (AMPs) through the microbe-specific activation of the Toll or the Imd signaling pathway. Upon systemic infection, the production of AMPs is both positively a ...

Ubiquitination of proteins by the Nedd4 family of ubiquitin ligases is a significant mechanism in protein trafficking and degradation and provides for tight spatiotemporal regulation. Ubiquitination is gaining increasing recognition as a central mechanism ...

In numerous biological processes that constitute the base of living organisms, protein function is fundamentally related to internal dynamics occurring on μs-ms time scales that can give rise to chemical exchange contributions to relaxation. In a heteronuc ...

The interaction between oxaliplatin and the model protein ubiquitin (Ub) was investigated in a top-down approach by means of high-resolution electrospray ionization mass spectrometry (ESI-MS) using diverse tandem mass spectrometric (MS/MS) techniques, incl ...

R6/2 transgenic mice with expanded CAG repeats (> 300) have a surprisingly prolonged disease progression and longer lifespan than prototypical parent R6/2 mice (carrying 150 CAGs); however, the mechanism of this phenotype amelioration is unknown. We compar ...

Chemical Ligand Space of Cereblon

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The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for degradation

A chemical biology approach to decipher chromatin ubiquitylation by RNF168

Coordination of protein synthesis and degradation in mammalian cells

Gentle nano-electrospray ion source for reliable and efficient generation of microsolvated ions

Intrinsically High Capacity of Animal Cells From a Symbiotic Cnidarian to Deal With Pro-Oxidative Conditions

Endoplasmic Reticulum and Lysosomal Quality Control of Four Nonsense Mutants of Iduronate 2-Sulfatase Linked to Hunter's Syndrome

Selective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains

Targeted protein degradation through cytosolic delivery of monobody binders using bacterial toxins

DNA repair protein Rad18 restricts LINE-1 mobility

Dynamic protein-chromatin interactions in heterochromatin and during the DNA damage response on the single molecule level

Single Live Cell Monitoring of Protein Turnover Reveals Intercellular Variability and Cell-Cycle Dependence of Degradation Rates

Cytosolic delivery and characterization of monobodies interfering with SH2 domain-phosphotyrosine interactions

Biochemical and biophysical characterization of ruthenation of BRCA1 RING protein by RAPTA complexes and its E3 ubiquitin ligase activity

Ubiquitin-dependent folding of the Wnt signaling coreceptor LRP6

RETRACTED: Autoadaptive ER-Associated Degradation Defines a Preemptive Unfolded Protein Response Pathway

dRYBP Contributes to the Negative Regulation of the Drosophila Imd Pathway

Nedd4 and Nedd4-2: Ubiquitin ligases at work in the neuron

Dynamic Studies through Control of Relaxation in NMR Spectroscopy

Fragmentation methods on the balance: unambiguous top–down mass spectrometric characterization of oxaliplatin–ubiquitin binding sites

Gene expression profiling of R6/2 transgenic mice with different CAG repeat lengths reveals genes associated with disease onset and progression in Huntington's disease