Abstract
Human Fas-associated factor 1 (hFAF1) is a novel protein having multiubiquitin-related domains. We investigated the cellular functions of hFAF1 and found that valosin-containing protein (VCP), the multiubiquitin chain-targeting factor in the degradation of the ubiquitin-proteasome pathway, is a binding partner of hFAF1. hFAF1 is associated with the ubiquitinated proteins via the newly identified N-terminal UBA domain and with VCP via the C-terminal UBX domain. The overexpression of hFAF1 and a truncated UBA domain inhibited the degradation of ubiquitinated proteins and increased cell death. These results suggest that hFAF1 binding to ubiquitinated protein and VCP is involved in the ubiquitin-proteasome pathway. We hypothesize that hFAF1 may serve as a scaffolding protein that regulates protein degradation in the ubiquitin-proteasome pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adenosine Triphosphatases
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Amino Acid Sequence
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Apoptosis
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Apoptosis Regulatory Proteins
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Carrier Proteins / analysis
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Carrier Proteins / metabolism
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Carrier Proteins / physiology*
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Cell Cycle Proteins / analysis
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Cell Cycle Proteins / metabolism*
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Cell Line
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Cytosol / chemistry
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Cytosol / metabolism
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Humans
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I-kappa B Proteins / metabolism
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Leupeptins / pharmacology
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Molecular Sequence Data
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NF-KappaB Inhibitor alpha
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Proteasome Endopeptidase Complex / physiology*
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Proteasome Inhibitors
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Protein Structure, Tertiary / physiology
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Tumor Necrosis Factor-alpha / pharmacology
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Ubiquitin / metabolism*
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Valosin Containing Protein
Substances
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Adaptor Proteins, Signal Transducing
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Apoptosis Regulatory Proteins
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Carrier Proteins
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Cell Cycle Proteins
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FAF1 protein, human
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I-kappa B Proteins
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Leupeptins
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NFKBIA protein, human
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Proteasome Inhibitors
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Tumor Necrosis Factor-alpha
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Ubiquitin
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NF-KappaB Inhibitor alpha
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Proteasome Endopeptidase Complex
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Adenosine Triphosphatases
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VCP protein, human
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Valosin Containing Protein
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benzyloxycarbonylleucyl-leucyl-leucine aldehyde