Human Fas-associated factor 1, interacting with ubiquitinated proteins and valosin-containing protein, is involved in the ubiquitin-proteasome pathway.
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.
Song
Eun Joo
EJ
Center for Cell Signaling Research, Division of Molecular Life Sciences and College of Pharmacy, Ewha Womans University, Seoul 120-750, South Korea.
Yim
Seung-Hee
SH
Kim
Eunhee
E
Kim
Nam-Soon
NS
Lee
Kong-Joo
KJ
D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000032:analysis / Q000378:metabolism*; D002460:Cell Line; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D008969:Molecular Sequence Data; D000072000:NF-KappaB Inhibitor alpha; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D061988:Proteasome Inhibitors; D017434:Protein Structure, Tertiary / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D025801:Ubiquitin / Q000378:metabolism*; D000074405:Valosin Containing Protein
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C490780:FAF1 protein, human; D020672:I-kappa B Proteins; D007976:Leupeptins; C000606204:NFKBIA protein, human; D061988:Proteasome Inhibitors; D014409:Tumor Necrosis Factor-alpha; D025801:Ubiquitin; D000072000:NF-KappaB Inhibitor alpha; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
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