A short binding site in the KPC1 ubiquitin ligase mediates processing of NF-κB1 p105 to p50: A potential for a tumor-suppressive PROTAC
Copyright policy )A short binding site in the KPC1 ubiquitin ligase mediates processing of NF-κB1 p105 to p50: A potential for a tumor-suppressive PROTAC
Significance Accumulation of abnormal proteins underlies the mechanisms of numerous diseases such as malignancies and neurodegeneration. A recent development makes use of the UPS to remove such proteins. Small molecules (PROTACs) that are made of two heads—one that binds to a “universal” Ub ligase and the other that binds to the target substrate—bring the two together, which results in ubiquitination and subsequent proteasomal degradation of the target. We designed a PROTAC made of the pVHL ligase ligand and the short site of the KPC1 ligase that binds the p105 NF-ĸB precursor. The PROTAC mimics the enzymatic activity of the native KPC1 and can therefore serve as a prototype for the development of a tumor-suppressive drug.
Proteasome Endopeptidase Complex, Binding Sites, Ubiquitin, Ubiquitin-Protein Ligases, NF-kappa B, Transcription Factor RelA, Ubiquitination, NF-kappa B p50 Subunit, Cell Line, Tumor, Neoplasms, Proteolysis, Humans, Protein Processing, Post-Translational, Cell Proliferation, Peptide Hydrolases, Protein Binding, Signal Transduction
Proteasome Endopeptidase Complex, Binding Sites, Ubiquitin, Ubiquitin-Protein Ligases, NF-kappa B, Transcription Factor RelA, Ubiquitination, NF-kappa B p50 Subunit, Cell Line, Tumor, Neoplasms, Proteolysis, Humans, Protein Processing, Post-Translational, Cell Proliferation, Peptide Hydrolases, Protein Binding, Signal Transduction
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).8 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!