{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kanack AJ"],"funding":["National Institute of Neurological Disorders and Stroke","NINDS NIH HHS","National Institute of General Medical Sciences","NIGMS NIH HHS"],"pagination":["e202100633"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9016715"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["23(6)"],"pubmed_abstract":["The ubiquitin ligase C-terminus of Hsc70 interacting protein (CHIP) is an important regulator of proteostasis. Despite playing an important role in maintaining proteostasis, little progress has been made in developing small molecules that regulate ubiquitin transfer by CHIP. Here we used differential scanning fluorimetry to identify compounds that bound CHIP. Compounds that bound CHIP were then analyzed by quantitative ubiquitination assays to identify those that altered CHIP function. One compound, MS.001, inhibited both the chaperone binding and ubiquitin ligase activity of CHIP at low micromolar concentrations. Interestingly, we found that MS.001 did not have activity against isolated U-box or tetratricopeptide (TPR) domains, but instead only inhibited full-length CHIP. Using in silico "],"journal":["Chembiochem : a European journal of chemical biology"],"pubmed_title":["Chemical Regulation of the Protein Quality Control E3 Ubiquitin Ligase C-Terminus of Hsc70 Interacting Protein (CHIP)."],"pmcid":["PMC9016715"],"funding_grant_id":["R01 NS112191","R01NS112191","R35 GM119544","R35 GM128840","R35GM119544"],"pubmed_authors":["Olp MD","Gooden DM","McMahon K","Smith BC","Scaglione KM","Newsom OJ","Scaglione JB","Kanack AJ"],"additional_accession":[]},"is_claimable":false,"name":"Chemical Regulation of the Protein Quality Control E3 Ubiquitin Ligase C-Terminus of Hsc70 Interacting Protein (CHIP).","description":"The ubiquitin ligase C-terminus of Hsc70 interacting protein (CHIP) is an important regulator of proteostasis. Despite playing an important role in maintaining proteostasis, little progress has been made in developing small molecules that regulate ubiquitin transfer by CHIP. Here we used differential scanning fluorimetry to identify compounds that bound CHIP. Compounds that bound CHIP were then analyzed by quantitative ubiquitination assays to identify those that altered CHIP function. One compound, MS.001, inhibited both the chaperone binding and ubiquitin ligase activity of CHIP at low micromolar concentrations. Interestingly, we found that MS.001 did not have activity against isolated U-box or tetratricopeptide (TPR) domains, but instead only inhibited full-length CHIP. Using in silico ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2026-05-09T22:38:51.336Z","creation":"2025-02-19T03:26:45.062Z"},"accession":"S-EPMC9016715","cross_references":{"pubmed":["35061295"],"doi":["10.1002/cbic.202100633"]}}