In order to permit reversible and adjustable modulation, we have created a CAR that is capable of on-demand downregulation by fusing the CAR to a previously developed ligand-induced degradation (LID) domain. Addition of a small molecule ligand triggers exposure of a cryptic degron within the ...
Heterobifunctional small-molecule degraders that induce protein degradation through ligase-mediated ubiquitination have shown considerable promise as a new pharmacological modality. However, we currently lack a detailed understanding of the molecular bas
4 A, ligand-induced down-regulation was largely inhibited by all three proteasome inhibitors but was not affected by calpain inhibitor II. In addition to the inhibition of the ligand-induced degradation, basal levels of PPARγ are increased by the presence of the proteasome inhibitors for the ...
(Fig.2a)23. Ligands2and8were connected by a variety of different linkers (Supplementary Fig.2a). All bifunctional probes induced degradation of BET proteins BRD2, 3 and 4 in Jurkat cells at 3 µM after 6 h treatment. Compounds9and10showed potent degradation activity, and were chosen...
Ligand-induced down-regulation of the type I interferon receptor represents a major mechanism of negative regulation of signaling and involves internalization and lysosomal degradation of IFNAR1. Interferon {alpha} promotes phosphorylation of IFNAR1 on serine 535, followed by recruitment of the {beta}...
NMR spectroscopy results show that the rigid protein matrix provides a frame for fast substrate binding in multiple conformations, accompanied by slow conversion, attributed to an enzyme induced substrate distortion. A model is proposed in which the rigid enzyme takes advantage of substrate flexibility ...
EphrinA1-EphA2 interaction-mediated apoptosis and FMS-like tyrosine kinase 3 receptor ligand-induced immunotherapy inhibit tumor growth in a breast cancer mouse model. Tandon Manish,Vemula Sai V,Sharma Anurag,Ahi Yadvinder S,Mittal Shalini,Bangari Dinesh S,Mittal Suresh K. The journal of gene ...
Ligand-inducedendocytosisandnuclear localizationofangiotensinIIreceptors expressedinCHOcells 1 DepartamentodeBiofísica,EscolaPaulistadeMedicina, UniversidadeFederaldeSãoPaulo,SãoPaulo,SP,Brasil 2 LaboratóriodeBiologiaMolecular,InstitutodoCoração, FaculdadedeMedicina,UniversidadedeSãoPaulo,SãoPaulo,SP,Brasil ...
SW III-123 induced rapid degradation of inhibitor of apoptosis proteins (cIAP1 and cIAP2), accumulation of NF-kappa B-inducing kinase (NIK) and phosphorylation of NF-kappa B p65, suggesting that SW III-123 activated both canonical and noncanonical NF-kappa B pathways in SKOV-3 cells. SW ...
Functional properties of leptin receptor isoforms: internalization and degradation of leptin and ligand-induced receptor downregulation. Uotani S, Bjorbaek C, Tornoe J, Flier JS: Functional properties of leptin receptor isoforms: internalization and degradation of leptin and ligand- induced... S Uotani...