Ubiquitination/ Proteasome
Ubiquitination is a process in targeting proteins for degradation by the proteasome. Ubiquitin (Ub) is a 76 amino acid polypeptide which can be covalently attached to various cellular proteins by the ubiquitination process. This ubiquitin-proteasome system plays a vital role in cell division, growth, differentiation, transcriptional regulation, apoptosis and immunity etc. Three main types of enzymes are involved in the process of ubiquitination. In the first step, activation of ubiquitin is carried out by ubiquitin-activating enzyme (E1) through an ATP-dependent reaction. In the second step, the activated ubiquitin is transferred from E1 to ubiquitin-conjugating enzyme (E2). In the final step, the ubiquitin protein ligase (E3) is required for labeling the ubiquitin to target substrate protein. An isopeptide bond is formed between the carboxyl terminus of ubiquitin and the ε-amino group of a lysine residue in the target protein.
Once the substrate protein is labeled, proteasome will bind to a polyubiquitin chain, allowing the degradation of the labeled protein. The polyubiquitinated target protein is then recognized and degraded by the 26S proteasome. Deubiquitinating enzymes (DUBs) reverse the process of ubiquitination by removing ubiquitin from its substrate protein. Dysregulation of the ubiquitin-proteasome system has been linked to cancer, diabetes, cardiovascular and neurodegenerative diseases etc.
- B6032 CB-5083Target: p97Summary: p97 inhibitor
- B2151 STF-62247Target: AutophagySummary: Autophagy inducer in renal cell
- A4443 Gliotoxin1 CitationTarget: 20S proteasomal chymotrypsin|Geranylgeranyltransferase I|FarnesyltransferaseSummary: 20S proteasome inhibitor
- A4429 Vialinin ATarget: Deubiquitinating enzymes (DUBs)|IL Receptors|CCL2Summary: USP/isopeptidase T (IsoT)/UCH-L1 DUB inhibitor
- A3966 Doxorubicin3 CitationSummary: Topo II inhibitor,immunosuppresive antineoplastic antibiotic
- A8212 PR-619Target: Deubiquitinating enzymes (DUBs)Summary: Deubiquitylating enzymes (DBUs) inhibitor
- A8250 LY 29400216 CitationTarget: PI3KSummary: Potent PI3K inhibitor
- A2845 OmeprazoleSummary: H+,K+-ATPase inhibitor
- A2324 Dexamethasone (DHAP)Target: interleukin receptorSummary: Glucocorticoidan; anti-inflammatory
- A8323 WP11301 CitationSummary: Deubiquitinase (DUB) inhibitor, Cell permeable