title: Dioxin receptor is a ligand-dependent E3 ubiquitin ligase.
abstract: Fat-soluble ligands, including sex steroid hormones and environmental toxins, activate ligand-dependent DNA-sequence-specific transcriptional factors that transduce signals through target-gene-selective transcriptional regulation. However, the mechanisms of cellular perception of fat-soluble ligand signals through other target-selective systems remain unclear. The ubiquitin-proteasome system regulates selective protein degradation, in which the E3 ubiquitin ligases determine target specificity. Here we characterize a fat-soluble ligand-dependent ubiquitin ligase complex in human cell lines, in which dioxin receptor (AhR) is integrated as a component of a novel cullin 4B ubiquitin ligase complex, CUL4B(AhR). Complex assembly and ubiquitin ligase activity of CUL4B(AhR) in vitro and in vivo are dependent on the AhR ligand. In the CUL4B(AhR) complex, ligand-activated AhR acts as a substrate-specific adaptor component that targets sex steroid receptors for degradation. Thus, our findings uncover a function for AhR as an atypical component of the ubiquitin ligase complex and demonstrate a non-genomic signalling pathway in which fat-soluble ligands regulate target-protein-selective degradation through a ubiquitin ligase complex.
authors: ERATO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors: Fumiaki
authors: F
authors: Ohtake
authors: Atsushi
authors: A
authors: Baba
authors: Ichiro
authors: I
authors: Takada
authors: Maiko
authors: M
authors: Okada
authors: Kei
authors: K
authors: Iwasaki
authors: Hiromi
authors: H
authors: Miki
authors: Sayuri
authors: S
authors: Takahashi
authors: Alexander
authors: A
authors: Kouzmenko
authors: Keiko
authors: K
authors: Nohara
authors: Tomoki
authors: T
authors: Chiba
authors: Yoshiaki
authors: Y
authors: Fujii-Kuriyama
authors: Shigeaki
authors: S
authors: Kato
mesh_terms: D002460:Cell Line; D044842:Cullin Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D006801:Humans; D008024:Ligands; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D015533:Transcriptional Activation
chemical_list: C517832:CUL4B protein, human; D044842:Cullin Proteins; D047628:Estrogen Receptor alpha; D008024:Ligands; D046912:Multiprotein Complexes; D018336:Receptors, Aryl Hydrocarbon