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Ubiquitin E3 ligases (EC 188.8.131.52) attach ubiquitin molecules onto lysine residues of proteins in order to target the protein for a specific cellular process, such as proteasomal degradation or an alteration in subcellular localization.
|Cat No||Product Name / Activity|
|High affinity Smurf1 inhibitor; enhances BMP signaling|
|Cdc20 inhibitor; inhibits Cdc20-substrate interaction|
|6157||cis VH 298|
|Negative control for VH 298|
|β-TrCP1 ligase inhibitor|
|HECT E3 ubiquitin ligase inhibitor|
|Hdm2 inhibitor; activates p53-dependent transcription|
|MDM2 antagonist. Disrupts MDM2-p53 interaction|
|MDM2 antagonist; inhibits MDM2-p53 interaction|
|MDM2 antagonist; active enantiomer of Nutlin-3 (Cat. No. 3984)|
|Cereblon ubiquitination inhibitor; also TNF-α inhibitor and antiangiogenic|
|Inhibitor of Bmi1/Ring1A; blocks histone H2A ubiquitination|
|Bmi-1 inhibitor; antitumor|
|MDM2-p53 interaction inhibitor|
|Inhibits Skp2-mediated p27 degradation; induces cell cycle arrest|
|Selective inhibitor of E3 ubiquitin ligase|
|High affinity MDM2 inhibitor|
|Selective Skp2 inhibitor; suppresses E3 ligase activity|
|Ubiquitin ligase APC/C inhibitor; promotes Cdc20 autoubiquitination|
|Binds cereblon, inhibiting ubiquitin ligase activity; alsoTNF-a synthesis inhibitor|
|High-affinity inhibitor of VHL|
|Cat No||Product Name / Activity|
|(+)-JQ1 based PROTAC with selectivity for BRD4|
|6155||cis MZ 1|
|Negative Control for MZ1|
|(+)-JQ1 based PROTAC that selectively degrades BET bromodomains in cells|
|Cereblon binder; induces ubiquitination and degradation of CK1α by E3 ubiquitin ligase|
|(+)-JQ1 based PROTAC that selectively degrades BRD4 in cells|
|Protects against α-synuclein toxicity; promotes Rsp5/Nedd4-dependent endosomal transport|
|Protects against MDM2-mediated p53 degradation|
Ubiquitin E3 ligases (EC 184.108.40.206) attach ubiquitin molecules onto lysine residues of proteins in order to target the protein for a specific cellular process, such as proteasomal degradation or an alteration in subcellular localization. In addition to the specific ubiquitin ligases such as MDM2, E3A and anaphase-promoting complex (APC), many other proteins also contain domains that possess ubiquitin ligase activity. Almost all known ubiquitin E3 ligases contain one of three domains: a HECT, RING or A20-type zinc finger domain. Hundreds of E3 ligases have been identified so far, and their relative abundance in comparison to E1 and E2 enzymes is thought to confer specificity to the process of ubiquitination.
Ubiquitin ligases function in a complex with an E1-activating enzyme, an E2-conjugating enzyme and an E3 ubiquitin ligase. Using ATP, E1 activates the ubiquitin molecule and transfers it to E2. E2 interacts with E3 partners to transfer the ubiquitin moeity to the target protein. Generally multiple ubiquitin molecules are attached to a protein, in a process known as polyubiquitination, but the addition of single ubiquitin molecules ('monoubiquitination') may also occur within cells.
The ubiquitin ligase MDM2 is best known for its negative regulation of the tumor suppressor p53. It does this in two ways: by binding the N-terminal of p53 and inhibiting transcriptional activation; and by targeting p53 for degradation by the 26S proteasome. The latter is accomplished by polyubiquitination of p53, a consequence of MDM2's E3 ubiquitin ligase activity. Due to its inhibition of tumor suppressor activity, MDM2 is considered to be an oncoprotein, and therefore a cancer target. MDM2 may also ubiquitinate itself, though this can be reversed by the activity of USP7 (ubiquitin-specific protease 7). When DNA damage is evident, however, MDM2 is phosphorylated by ATM kinase; this lowers its affinity for USP7, permits its proteasomal degradation, and enables p53-mediated DNA repair.
Tocris offers the following scientific literature for Ubiquitin E3 Ligases to showcase our products. We invite you to request* or download your copy today!
*Please note that Tocris will only send literature to established scientific business / institute addresses.
There are two currently recognized forms of programmed cell death: apoptosis and necroptosis. This poster summarizes the signaling pathways involved in apoptosis, necroptosis and cell survival following death receptor activation, and highlights the influence of the molecular switch, cFLIP, on cell fate.