Access

Letter

Nature 446, 562-566 (29 March 2007) | doi:10.1038/nature05683; Received 13 December 2006; Accepted 16 February 2007

Open Innovation Challenges

naturejobs

Dioxin receptor is a ligand-dependent E3 ubiquitin ligase

Fumiaki Ohtake1,2, Atsushi Baba2, Ichiro Takada2, Maiko Okada2, Kei Iwasaki1, Hiromi Miki2, Sayuri Takahashi2,3, Alexander Kouzmenko1,2, Keiko Nohara4, Tomoki Chiba5, Yoshiaki Fujii-Kuriyama6,7 & Shigeaki Kato1,2

  1. ERATO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
  2. Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
  3. Department of Urology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan
  4. National Institute for Environmental Studies, Tsukuba, Ibaraki 305-8506, Japan
  5. Graduate School of Life and Environmental Sciences, and,
  6. TARA Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8577, Japan
  7. SORST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan

Correspondence to: Shigeaki Kato1,2 Correspondence and requests for materials should be addressed to S.K. (Email: uskato@mail.ecc.u-tokyo.ac.jp).

Top

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 regulation1. 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 specificity2, 3, 4. 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 ubiquitin ligase complex, CUL4BAhR. Complex assembly and ubiquitin ligase activity of CUL4BAhR in vitro and in vivo are dependent on the AhR ligand. In the CUL4BAhR 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.

  1. ERATO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
  2. Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
  3. Department of Urology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan
  4. National Institute for Environmental Studies, Tsukuba, Ibaraki 305-8506, Japan
  5. Graduate School of Life and Environmental Sciences, and,
  6. TARA Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8577, Japan
  7. SORST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan

Correspondence to: Shigeaki Kato1,2 Correspondence and requests for materials should be addressed to S.K. (Email: uskato@mail.ecc.u-tokyo.ac.jp).

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

NEWS AND VIEWS

Chemical biology A degrading solution to pollution

Nature News and Views (29 Mar 2007)

Eggs in the balance

Nature Genetics News and Views (01 Aug 2001)