Jul 1, 2017 · Unlike typical CUL4B DCFA E3 ubiquitin ligases, which contain damaged DNA binding protein 1 (DDB1)- and CUL4-associated factors (DCFA), the CUL4 AhR complex uses the activated AhR as an adaptor protein for substrate recognition.

Mar 29, 2007 · Here we characterize a fat-soluble ligand-dependent ubiquitin ligase complex in human cell lines, in which dioxin receptor (AhR) 5, 6, 7, 8, 9 is integrated as a component of a novel cullin 4B...

We will compare CUL4’s pleiotropic functions across several species, and review the current model for CUL4 assembly with its linker protein DDB1 (for damaged DNA binding) and its family of WD40 containing substrate receptors.

Feb 15, 2009 · AhR has recently been shown to promote the proteolysis of ERα/AR through assembling a ubiquitin ligase complex, CUL4B AhR. In the CUL4B AhR complex, AhR acts as a substrate-recognition subunit to recruit ERα/AR. This action defines a novel role for AhR as a ligand-dependent E3 ubiquitin ligase.

Our findings establish a critical role of AhR in regulating PPARγ stability and suggest that the AhR–PPARγ interaction may represent a potential therapeutic target for managing metabolic diseases arising from PPARγ dysfunction.

Nov 1, 2019 · For ubiquitin ligase activity, AhR directly binds to cullin 4B (CUL4B) as an adaptor protein, and this Cul4B/AhR complex includes DDB1, Rbx1, and TBL3. AhR also targeted β-catenin as an ubiquitination substrate, and AhR deficient mice have spontaneously developed cecal tumors as the result of β-catenin accumulation [ 16 ].

Nov 30, 2020 · Here, we have shown that ARNT interacts with DDB1 and CUL4-associated factor 15 (DCAF15), and the aryl sulfonamides, indisulam and E7820, induce its proteasomal degradation through Cullin-RING finger ligase 4 containing DCAF15 (CRL4 DCAF15) E3 ligase.

Ddb1 silencing activates Trp53 pathway and leads to significant effects on cell cycle progression and rapid apoptosis. The abrogation of hematopoietic progenitor cells can be partially rescued by simultaneous deletion of Trp53.

Here, we studied the role of two enzymes reported to enhance AHR breakdown: the cullin 4B (CUL4B) AHR complex, an E3 ubiquitin ligase that targets the AHR and other proteins for ubiquitination, and TiPARP, which targets proteins for ADP-ribosylation, a posttranslational modification that can increase susceptibility to degradation.

As expected, the components of AhR complex, including endogenous CUL4B, DDB1, and ROC1, were detected in the affinity-purified fractions, thereby forming CRL4B AhR E3 complex (Fig. 3H).