The BTB protein MEL-26 is a substrate-specific adaptor of the CUL-3 ubiquitin-ligase

Nature. 2003 Sep 18;425(6955):311-6. doi: 10.1038/nature01959. Epub 2003 Sep 3.


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-ligases. 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 transition. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Alleles
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism*
  • Cullin Proteins*
  • Ligases / chemistry*
  • Ligases / metabolism*
  • Macromolecular Substances
  • Meiosis
  • Microtubules / metabolism
  • Mitosis
  • Molecular Sequence Data
  • Mutation / genetics
  • Protein Binding
  • Protein Subunits / metabolism
  • RNA Interference
  • Substrate Specificity
  • Ubiquitin-Protein Ligases


  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cullin Proteins
  • Macromolecular Substances
  • Mel-26 protein, C elegans
  • Protein Subunits
  • Ubiquitin-Protein Ligases
  • Adenosine Triphosphatases
  • MEI-1 protein, C elegans
  • Ligases