Protein modification by the attachment of ubiquitin to cellular proteins is a key mechanism in regulating many cellular and organismal processes. Ubiquitin is covalently attached to target proteins via an isopeptide bond between the C-terminus of ubiquitin and a lysine residue of the acceptor substrate. Additional ubiquitins can be conjugated to any of the 7 lysine residues of ubiquitin or to its more ..
Target
Depositor Specified Assays
| AID | Name | Type | Comment |
|---|---|---|---|
| 651999 | uHTS identification of small molecule inhibitors of Csn-mediated Deneddylation of Cullin-Ring Ligases, vis a fluorescence polarization assay | screening |
Description:
Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG)
Source Affiliation: Sanford Burnham Medical Research Institute, La Jolla, CA
Network: NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Number: 1 R21 NS071527-01A1
Assay Provider: Dr. Raymond Deshaies, California Institute of Technology
Protein modification by the attachment of ubiquitin to cellular proteins is a key mechanism in regulating many cellular and organismal processes. Ubiquitin is covalently attached to target proteins via an isopeptide bond between the C-terminus of ubiquitin and a lysine residue of the acceptor substrate. Additional ubiquitins can be conjugated to any of the 7 lysine residues of ubiquitin or to its N-terminus to form a polyubiquitin chain on the substrate. Assembly of a chain of >=4 ubiquitins linked together via Lys48 of ubiquitin marks cellular proteins for degradation by the 26S proteasome. Ubiquitination of proteins is achieved through an enzymatic cascade involving ubiquitin-activating (E1), ubiquitin-conjugating (E2), and ubiquitin-ligating (E3) enzymes. Ubiquitination occurs when an E3 binds to both substrate and an E2 thioesterified with ubiquitin (E2~Ub), bringing them in proximity so that the ubiquitin is transferred from E2 to substrate.
Among the most intensively studied E3s are members of the cullin-RING ligase (CRL) superfamily, which are regulated by a reversible covalent modification of the cullin with the ubiquitin-like protein, Nedd8. Deconjugation of Nedd8 from cullins is carried out by a novel metalloisopeptidase in the Csn5 subunit of the COP9/Signalosome (CSN). Csn5 appears to be the only enzyme capable of cleaving Nedd8 from Cul1 in vivo.
CSN is an excellent candidate for the development of a small molecule inhibitor because such a compound would greatly facilitate cell biological studies of this key regulatory factor.
Source Affiliation: Sanford Burnham Medical Research Institute, La Jolla, CA
Network: NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Number: 1 R21 NS071527-01A1
Assay Provider: Dr. Raymond Deshaies, California Institute of Technology
Protein modification by the attachment of ubiquitin to cellular proteins is a key mechanism in regulating many cellular and organismal processes. Ubiquitin is covalently attached to target proteins via an isopeptide bond between the C-terminus of ubiquitin and a lysine residue of the acceptor substrate. Additional ubiquitins can be conjugated to any of the 7 lysine residues of ubiquitin or to its N-terminus to form a polyubiquitin chain on the substrate. Assembly of a chain of >=4 ubiquitins linked together via Lys48 of ubiquitin marks cellular proteins for degradation by the 26S proteasome. Ubiquitination of proteins is achieved through an enzymatic cascade involving ubiquitin-activating (E1), ubiquitin-conjugating (E2), and ubiquitin-ligating (E3) enzymes. Ubiquitination occurs when an E3 binds to both substrate and an E2 thioesterified with ubiquitin (E2~Ub), bringing them in proximity so that the ubiquitin is transferred from E2 to substrate.
Among the most intensively studied E3s are members of the cullin-RING ligase (CRL) superfamily, which are regulated by a reversible covalent modification of the cullin with the ubiquitin-like protein, Nedd8. Deconjugation of Nedd8 from cullins is carried out by a novel metalloisopeptidase in the Csn5 subunit of the COP9/Signalosome (CSN). Csn5 appears to be the only enzyme capable of cleaving Nedd8 from Cul1 in vivo.
CSN is an excellent candidate for the development of a small molecule inhibitor because such a compound would greatly facilitate cell biological studies of this key regulatory factor.
Protocol
See pertinent AIDs: 651999
Comment
Probe molecules are defined as the positives of this assay and assigned a score of 100. Testing has not progressed to the point where a probe molecule has been identified.
Additional Information
Grant Number: 1 R21 NS071527-01A1
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