Ubiquitin

The ubiquitin-proteasome system (UPS) targets numerous cellular proteins for degradation. It is a highly complex, temporally controlled, and tightly regulated process that plays major roles in a variety of basic cellular processes[1]. Degradation of a protein via the ubiquitin-proteasome pathway involves two discrete and successive steps: (1) tagging of the substrate by covalent attachment of multiple ubiquitin molecules to synthesize the polyubiquitin chain proteolytic signal and (2) degradation of the tagged protein by the 26S proteasome complex with release of free and reusable ubiquitin catalyzed by ubiquitin-recycling enzymes (DUBs)[2]. Conjugation of ubiquitin to the protein substrate proceeds via a three-step cascade mechanism. Initially, the ubiquitin-activating enzyme E1 activates ubiquitin in an ATP-requiring reaction resulting in a high-energy thiol ester intermediate. Subsequently, this intermediate is transferred to a member of the ubiquitin-carrier proteins family of enzymes, E2 (also known as a ubiquitin-conjugating enzyme [UBC]). Finally, from E2, the activated ubiquitin moiety is attached to the substrate that is specifically bound to an E3, a member of the ubiquitin-protein ligase family of proteins[3]. By successively adding additional activated ubiquitin moieties to internal Lys residues on the previously conjugated ubiquitin molecule, a polyubiquitin chain is synthesized. The degradation signal that is recognized by the 26S proteasome complex is made of a Lys48 polyubiquitin chain. In contrast, monoubiquitination or polyubiquitination with chains linked together via Lys63 serve as nonproteolytic signals in intracellular trafficking, DNA repair, activation of transcription and other signal transduction pathways[4].


[1] Drug discovery in the ubiquitin–proteasome system. G. Nalepa, M. Rolfe, J.W.Harper. Nature Reviews Drug Discovery2006, 5, 596-613.
[2] Mechanisms of Proteasome Inhibitor PS-341-induced G2-M-Phase Arrest and Apoptosis in Human Non-Small Cell Lung Cancer Cell Lines. Y Ling et al. Clin. Cancer Res. 2003, 9, 1145-1154.
[3] R.J. Deshaies, C.A.P. Joazeiro. RING Domain E3 Ubiquitin Ligases. Annu. Rev. Biochem. 2009, 78, 399-434.
[4] The Ubiquitin Proteasome System in Neurodegenerative Diseases: Sometimes the Chicken, Sometimes the Egg. A.Ciechanover, P. Brundin. Neuron 2003, 40, 427–446.

Items 1 to 15 of 59 total

per page
Page:
  1. 1
  2. 2
  3. 3
  4. 4
Axon ID Name Description From price
1639 YM 155 Survivin suppressant €95.00
1779 WP 1130 Deubiquitinase Inhibitor €95.00
2810 VH298 Inhibitor of E3 ubiquitin-protein ligase VHL €135.00
2991 USP7-USP47 inhibitor Selective inhibitor of deubiquitinase USP7 and USP47  Recently added €90.00
2333 TCID Potent inhibitor of UCHL3 with >100-fold selectivity over UCHL1 €80.00
2894 STF 62247 Inducer of apoptosis and autophagy in VHL-deficient RCC cells €85.00
2512 Spautin 1 Inhibitor of USP10 and USP13 and Beclin1 related autophagy €95.00
2437 SP 141 Specific MDM2 inhibitor with therapeutic effects in breast cancer models €120.00
2426 SMURF1 inhibitor A01 Inhibitor of E3 ubiquitin-protein ligase SMURF1 €115.00
1904 SMER 3 Inhibitor of an SCF family E3 Ubiquitin ligase €90.00
2244 SCH 529074 Small molecule activator of mutant p53. €100.00
1790 SC 66 Allosteric Akt inhibitor €70.00
2741 SAR405838 MDM2-p53 inhibitor €125.00
2165 S 12 Survivin inhibitor €105.00
2009 RITA Activates p53 through inhibition of MDM2 €105.00

Items 1 to 15 of 59 total

per page
Page:
  1. 1
  2. 2
  3. 3
  4. 4
Please wait...