BCL-3 degradation involves its polyubiquitination through a FBW7-independent pathway and its binding to the proteasome subunit PSMB1.

The oncogenic protein BCL-3 activates or represses gene transcription through binding with the NF-kappaB proteins p50 and p52 and is degraded through a phospho- and GSK3-dependent pathway. However, the mechanisms underlying its degradation remain poorly understood. Yeast two-hybrid analysis led to the identification of the proteasome subunit PSMB1 as a ...
BCL-3-associated protein. The binding of BCL-3 to PSMB1 is required for its degradation through the proteasome. Indeed, PSMB1-depleted cells are defective in degrading polyubiquitinated BCL-3. The N-terminal part of BCL-3 includes lysines 13 and 26 required for the Lys(48)-linked polyubiquitination of BCL-3. Moreover, the E3 ligase FBW7, known to polyubiquitinate a variety of substrates phosphorylated by GSK3, is dispensable for BCL-3 degradation. Thus, our data defined a unique motif of BCL-3 that is needed for its recruitment to the proteasome and identified PSMB1 as a key protein required for the proteasome-mediated degradation of a nuclear and oncogenic IkappaB protein.
Mesh Terms:
Cell Cycle Proteins, Cell Line, Cell Line, Tumor, F-Box Proteins, Fluorescent Antibody Technique, HeLa Cells, Humans, Immunoprecipitation, Lysine, NF-kappa B p50 Subunit, NF-kappa B p52 Subunit, Phosphorylation, Proteasome Endopeptidase Complex, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins, Signal Transduction, Transcription Factors, Two-Hybrid System Techniques, Ubiquitin-Protein Ligases, Ubiquitination
J. Biol. Chem.
Date: Aug. 13, 2010
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