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Cul4-RING E3 ubiquitin ligase complex

Definition

Target type: cellularcomponent

A ubiquitin ligase complex in which a cullin from the Cul4 family and a RING domain protein form the catalytic core; substrate specificity is conferred by an adaptor protein. [PMID:16792691, PMID:18223036, PMID:18552200]

The Cul4-RING E3 ubiquitin ligase complex is a multi-protein complex that plays a crucial role in regulating a wide variety of cellular processes, including DNA replication, cell cycle progression, and signal transduction. This complex consists of several core components:

**1. Cullin 4 (Cul4):** This protein serves as a scaffold, bringing together the other components of the complex and providing a platform for the assembly of the active ubiquitin ligase.

**2. RING finger protein (RBX1):** This protein binds to the C-terminus of Cul4 and recruits the E2 ubiquitin-conjugating enzyme, which is responsible for transferring ubiquitin molecules to the target protein.

**3. DDB1:** This protein acts as an adaptor, binding to a variety of substrate recognition modules (SRMs), such as DCAF1, DCAF2, and DCAF15, which determine the specificity of the E3 ligase for particular target proteins.

**4. Substrate recognition modules (SRMs):** These proteins bind to specific target proteins, thereby mediating the recruitment of the target protein to the Cul4-RING E3 ubiquitin ligase complex.

**5. E2 ubiquitin-conjugating enzyme:** This enzyme is responsible for transferring ubiquitin molecules from the E1 ubiquitin-activating enzyme to the target protein.

**Cellular Component:**

The Cul4-RING E3 ubiquitin ligase complex is localized to various cellular compartments, including the nucleus, cytoplasm, and centrosomes. Its localization can vary depending on the specific substrate recognition module involved. For example, the DCAF1-Cul4 complex is primarily localized to the nucleus, where it plays a role in regulating DNA replication and repair.

**Mechanism of Action:**

The Cul4-RING E3 ubiquitin ligase complex functions by targeting specific proteins for ubiquitination. Ubiquitination is a post-translational modification that involves the attachment of ubiquitin molecules to a target protein. This process can lead to a variety of cellular outcomes, including protein degradation, changes in protein activity, and alteration of protein localization.

**Regulation:**

The activity of the Cul4-RING E3 ubiquitin ligase complex is tightly regulated by various mechanisms, including post-translational modifications, protein-protein interactions, and cellular localization.

**Overall, the Cul4-RING E3 ubiquitin ligase complex is a highly versatile and important regulator of cellular processes. Its ability to target a wide range of proteins for ubiquitination enables it to play a crucial role in maintaining cellular homeostasis and responding to various cellular stresses.**'
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Proteins (2)

ProteinDefinitionTaxonomy
DNA damage-binding protein 1A DNA damage-binding protein 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q16531]Homo sapiens (human)
Cullin-4AA cullin-4A that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q13619]Homo sapiens (human)

Compounds (6)

CompoundDefinitionClassesRoles
thalidomide2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione : A dicarboximide that is isoindole-1,3(2H)-dione in which the hydrogen attached to the nitrogen is substituted by a 2,6-dioxopiperidin-3-yl group.

thalidomide : A racemate comprising equimolar amounts of R- and S-thalidomide.

Thalidomide: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.
phthalimides;
piperidones
pomalidomide3-aminophthalimidoglutarimide: structure in first sourcearomatic amine;
dicarboximide;
isoindoles;
piperidones
angiogenesis inhibitor;
antineoplastic agent;
immunomodulator
lenalidomidearomatic amine;
dicarboximide;
isoindoles;
piperidones
angiogenesis inhibitor;
antineoplastic agent;
immunomodulator
4-pyridin-4-yl-2-sulfanylidene-5,6,7,8-tetrahydro-1H-quinoline-3-carbonitrilebipyridines
jq1 compoundcarboxylic ester;
organochlorine compound;
tert-butyl ester;
thienotriazolodiazepine
angiogenesis inhibitor;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
bromodomain-containing protein 4 inhibitor;
cardioprotective agent;
ferroptosis inducer
MZ1organic molecular entity