The BTB protein MEL-26 is a substrate-specific adaptor of the CUL-3 ubiquitin-ligase
Lionel Pintard (),
John H. Willis,
Andrew Willems,
Jacque-Lynne F. Johnson,
Martin Srayko,
Thimo Kurz,
Sarah Glaser,
Paul E. Mains,
Mike Tyers,
Bruce Bowerman and
Matthias Peter ()
Additional contact information
Lionel Pintard: Institute of Biochemistry ETH
John H. Willis: University of Oregon
Andrew Willems: Univ. Toronto
Jacque-Lynne F. Johnson: University of Calgary
Martin Srayko: University of Calgary
Thimo Kurz: University of Oregon
Sarah Glaser: Institute of Biochemistry ETH
Paul E. Mains: University of Calgary
Mike Tyers: Univ. Toronto
Bruce Bowerman: University of Oregon
Matthias Peter: Institute of Biochemistry ETH
Nature, 2003, vol. 425, issue 6955, 311-316
Abstract:
Abstract Many biological processes, such as development and cell cycle progression are tightly controlled by selective ubiquitin-dependent degradation of key substrates. In this pathway, the E3-ligase recognizes the substrate and targets it for degradation by the 26S proteasome. The SCF (Skp1–Cul1–F-box) and ECS (Elongin C–Cul2–SOCS box) complexes are two well-defined cullin-based E3-ligases1,2,3. The cullin subunits serve a scaffolding function and interact through their C terminus with the RING-finger-containing protein Hrt1/Roc1/Rbx1, and through their N terminus with Skp1 or Elongin C, respectively. In Caenorhabditis elegans, the ubiquitin-ligase activity of the CUL-3 complex is required for degradation of the microtubule-severing protein MEI-1/katanin at the meiosis-to-mitosis transition4. However, the molecular composition of this cullin-based E3-ligase is not known. Here we identified the BTB-containing protein MEL-26 as a component required for degradation of MEI-1 in vivo. Importantly, MEL-26 specifically interacts with CUL-3 and MEI-1 in vivo and in vitro, and displays properties of a substrate-specific adaptor. Our results suggest that BTB-containing proteins may generally function as substrate-specific adaptors in Cul3-based E3-ubiquitin ligases.
Date: 2003
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DOI: 10.1038/nature01959
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