Abstract
Nbr1, a ubiquitous kinase scaffold protein, contains a PB1, and a ubiquitin-associated (UBA) domain. We show here that the nbr1 UBA domain binds to lysine-48 and -63 linked polyubiquitin-B chains. Nbr1 also binds to the autophagic effector protein LC3-A via a novel binding site. Ubiquitin-binding, but not PB1-mediated p62/SQSTM1 interaction, is required to target nbr1 to LC3 and polyubiquitin-positive bodies. Nbr1 binds additionally to proteins implicated in ubiquitin-mediated protein turnover and vesicle trafficking: ubiquitin-specific peptidases USP8, and the endosomal transport regulator p14/Robld3. Nbr1 thus contributes to specific steps in protein turnover regulation disrupted in several hereditary human diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autophagy / physiology*
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Binding Sites
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COS Cells
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Chlorocebus aethiops
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Endopeptidases / genetics
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Endopeptidases / metabolism
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Endosomal Sorting Complexes Required for Transport
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Humans
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In Vitro Techniques
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Intracellular Signaling Peptides and Proteins
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Ligands
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Lysine / chemistry
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Mice
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism*
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Polyubiquitin / metabolism*
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Protein Binding
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Protein Interaction Domains and Motifs
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Proteins / chemistry
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Proteins / genetics
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Proteins / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Two-Hybrid System Techniques
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Ubiquitin Thiolesterase / genetics
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Ubiquitin Thiolesterase / metabolism
Substances
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Endosomal Sorting Complexes Required for Transport
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Intracellular Signaling Peptides and Proteins
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Ligands
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MAP1LC3A protein, human
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Map1lc3b protein, mouse
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Microtubule-Associated Proteins
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NBR1 protein, human
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Nbr1 protein, mouse
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Proteins
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Recombinant Fusion Proteins
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Polyubiquitin
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Endopeptidases
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USP8 protein, human
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Ubiquitin Thiolesterase
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Lysine