Driver variants in orthogonal signaling pathways or in kinases downstream of the drug target can give rise to drug resistance in cancer. We observed rare gain-of-function variants arising from gRNAs predicted to
Membrane traffic operates by vesicles that bud from precursor organelles and are transported to their target compartment where they dock and fuse. Targeting requires tethering factors recruited by small GTPases and phosphoinositides whereas fusion is car
Patients with severe CKD (estimated GFR < 30 ml/min per 1.73 kg/m(2)) required significantly lower warfarin dosages (P = 0.0002), spent less time with their international normalized ratio within the target range (P = 0.049), and were at a higher risk for overanticoagulation (international...
Receptor-activated SMADs trimerize with SMAD4 to regulate context-dependent target gene expression. However, the presence of a single SMAD1/5/8 binding motif in cis-regulatory elements alone does not trigger transcription in native contexts. We hypothesize that binding to composite motifs in which ...
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Notably, perturbed genes in the known immunosuppressive WNT- and mammalian target of rapamycin-signaling pathway (WNT3; adjusted p = 0.015), and cell adhesion and extracellular matrix organization (LAMB4; adjusted p = 0.044), were also upregulated in non-responders compared with responders to ...
We use essential cookies to make sure the site can function. We also use optional cookies for advertising, personalisation of content, usage analysis, and social media. By accepting optional cookies, you consent to the processing of your personal data - including transfers to third parties. Some...
With these USP18 ABPs, we sought to perform competitive ABPP to evaluate target engagement and selectivity of DUB inhibitors (Fig.4A)41,42,52. Since USP18 does not efficiently react with Ub, USP18 is excluded in DUB inhibitor screening when using Ub-based probes, despite its biological impor...
Cleav- age of proteins and peptides could relate to target- ing host proteins such as those involved in defensive sieve-tube blocking as shown at least for the atypical extrafascicular phloem exudate of cucurbits [35]. Alternatively, although there is currently no direct evi- dence, exo...
When the cell is threatened by elevated oxidative stress, however, Keap1 undergoes modification and loses its ability to ubiquitinate Nrf2, allowing it to accumulate in the nucleus to induce the expression of its target genes31. Moreover, Keap1 was found to be able to bind Nestin, which is ...