Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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B-Cell Lymphoma 3 Protein
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Line
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Cell Line, Tumor
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F-Box Proteins / genetics
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F-Box Proteins / metabolism*
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F-Box-WD Repeat-Containing Protein 7
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Fluorescent Antibody Technique
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HeLa Cells
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Humans
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Immunoprecipitation
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Lysine / metabolism
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NF-kappa B p50 Subunit / genetics
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NF-kappa B p50 Subunit / metabolism
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NF-kappa B p52 Subunit / genetics
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NF-kappa B p52 Subunit / metabolism
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Phosphorylation / genetics
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Phosphorylation / physiology
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Proteasome Endopeptidase Complex / genetics
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Proteasome Endopeptidase Complex / metabolism*
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Protein Binding / genetics
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Protein Binding / physiology
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Protein Structure, Tertiary
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Signal Transduction / genetics
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Signal Transduction / physiology
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Two-Hybrid System Techniques
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / metabolism*
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Ubiquitination / genetics
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Ubiquitination / physiology
Substances
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B-Cell Lymphoma 3 Protein
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BCL3 protein, human
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Cell Cycle Proteins
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F-Box Proteins
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F-Box-WD Repeat-Containing Protein 7
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FBXW7 protein, human
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NF-kappa B p50 Subunit
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NF-kappa B p52 Subunit
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Proto-Oncogene Proteins
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Transcription Factors
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Ubiquitin-Protein Ligases
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Proteasome Endopeptidase Complex
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Lysine