Muf1, a novel Elongin BC-interacting leucine-rich repeat protein that can assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase.
The heterodimeric Elongin BC complex has been shown to interact in vitro and in mammalian cells with a conserved BC-box motif found in a growing number of proteins including RNA polymerase II elongation factor Elongin A, SOCS-box proteins, and the von Hippel-Lindau (VHL) tumor suppressor protein. Recently, the VHL-Elongin BC ... complex was found to interact with a module composed of Cullin family member Cul2 and RING-H2 finger protein Rbx1 to reconstitute a novel E3 ubiquitin ligase that activates ubiquitylation by the E2 ubiquitin-conjugating enzymes Ubc5 and Cdc34. In the context of the VHL ubiquitin ligase, Elongin BC functions as an adaptor that links the VHL protein to the Cul2/Rbx1 module, raising the possibility that the Elongin BC complex could function as an integral component of a larger family of E3 ubiquitin ligases by linking alternative BC-box proteins to Cullin/Rbx1 modules. In this report, we describe identification and purification from rat liver of a novel leucine-rich repeat-containing BC-box protein, MUF1, which we demonstrate is capable of assembling with a Cullin/Rbx1 module containing the Cullin family member Cul5 to reconstitute ubiquitin ligase activity. In addition, we show that the additional BC-box proteins Elongin A, SOCS1, and WSB1 are also capable of assembling with the Cul5/Rbx1 module to reconstitute potential ubiquitin ligases. Taken together, our findings identify MUF1 as a new member of the BC-box family of proteins, and they predict the existence of a larger family of Elongin BC-based E3 ubiquitin ligases.
Mesh Terms:
Amino Acid Sequence, Animals, Carrier Proteins, Cell Line, Cloning, Molecular, DNA, Complementary, Insects, Leucine, Ligases, Male, Membrane Proteins, Molecular Sequence Data, Protein Binding, Rats, Rats, Sprague-Dawley, Recombinant Proteins, Repetitive Sequences, Amino Acid, Sequence Homology, Amino Acid, Transcription Factors, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases, Ubiquitins
Amino Acid Sequence, Animals, Carrier Proteins, Cell Line, Cloning, Molecular, DNA, Complementary, Insects, Leucine, Ligases, Male, Membrane Proteins, Molecular Sequence Data, Protein Binding, Rats, Rats, Sprague-Dawley, Recombinant Proteins, Repetitive Sequences, Amino Acid, Sequence Homology, Amino Acid, Transcription Factors, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases, Ubiquitins
J. Biol. Chem.
Date: Aug. 10, 2001
PubMed ID: 11384984
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