Ubiquitin E3 Ligases

Ubiquitin E3 ligases (EC 6.3.2.19) 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.

Products
Background
Literature
Gene Data

Inhibitors

Cat No Product Name / Activity
5397 A01
High affinity Smurf1 inhibitor; enhances BMP signaling
5747 Apcin
Cdc20 inhibitor; inhibits Cdc20-substrate interaction
5636 GS 143
β-TrCP1 ligase inhibitor
5433 Heclin
HECT E3 ubiquitin ligase inhibitor
3503 HLI 373
Hdm2 inhibitor; activates p53-dependent transcription
2936 NSC 66811
MDM2 antagonist. Disrupts MDM2-p53 interaction
3984 Nutlin-3
MDM2 antagonist; inhibits MDM2-p53 interaction
6075 Nutlin 3a
MDM2 antagonist; active enantiomer of Nutlin-3 (Cat. No. 3984)
6302 Pomalidomide
Cereblon ubiquitination inhibitor; also TNF-α inhibitor and antiangiogenic
5047 PRT 4165
Inhibitor of Bmi1/Ring1A; blocks histone H2A ubiquitination
5191 PTC 209
Bmi-1 inhibitor; antitumor
2443 RITA
MDM2-p53 interaction inhibitor
4817 SKPin C1
Inhibits Skp2-mediated p27 degradation; induces cell cycle arrest
4375 SMER 3
Selective inhibitor of E3 ubiquitin ligase
5332 SP 141
High affinity MDM2 inhibitor
5076 SZL P1-41
Selective Skp2 inhibitor; suppresses E3 ligase activity
4506 TAME hydrochloride
Ubiquitin ligase APC/C inhibitor; promotes Cdc20 autoubiquitination
0652 Thalidomide
Binds cereblon, inhibiting ubiquitin ligase activity; alsoTNF-a synthesis inhibitor
6156 VH 298
High-affinity inhibitor of VHL
6719 YH 239-EE
MDM2 inhibitor; disrupts MDM2-p53 interaction

Controls

Cat No Product Name / Activity
6157 cis VH 298
Negative control for VH 298

Other

Cat No Product Name / Activity
6356 AT 1
(+)-JQ1 based PROTAC with selectivity for BRD4
6155 cis MZ 1
Negative Control for MZ1
6416 CM 11
Homo-PROTAC for self-degradation of pVHL30
6417 CMP 98
Negative Control for CM 11
6327 dBET1
(+)-JQ1 based PROTAC targeting BET bromodomains, active in vivo
6782 Indisulam
Molecular glue; pre-mRNA splicing modulator
6305 Lenalidomide
Cereblon binder; induces ubiquitination and degradation of CK1α by E3 ubiquitin ligase
6154 MZ 1
(+)-JQ1 based PROTAC that selectively degrades BRD4 in cells
5131 NAB 2
Protects against α-synuclein toxicity; promotes Rsp5/Nedd4-dependent endosomal transport
3365 Tenovin-1
Protects against MDM2-mediated p53 degradation
6524 TL 12-186
Multikinase degrading PROTAC
6525 TL 13-27
Negative control for TL 12-186

Ubiquitin E3 ligases (EC 6.3.2.19) 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.

External sources of pharmacological information for Ubiquitin E3 Ligases :

    Literature for Ubiquitin E3 Ligases

    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.


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    Ubiquitin E3 Ligase Gene Data

    Gene Species Gene Symbol Gene Accession No. Protein Accession No.
    MDM2 Human MDM2 NM_006880 Q00987
    Mouse Mdm2 NM_010786 P23804
    Rat Mdm2 NM_001108099 NP_001101569
    SKP2 Human SKP2 NM_005983 Q13309
    Mouse Skp2 NM_145468 Q9Z0Z3
    Rat Skp2 NM_001106416 NP_001099886