Human Fas-associated factor 1, interacting with ubiquitinated proteins and valosin-containing protein, is involved in the ubiquitin-proteasome pathway

Mol Cell Biol. 2005 Mar;25(6):2511-24. doi: 10.1128/MCB.25.6.2511-2524.2005.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adenosine Triphosphatases
  • Amino Acid Sequence
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Carrier Proteins / analysis
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Cytosol / chemistry
  • Cytosol / metabolism
  • Humans
  • I-kappa B Proteins / metabolism
  • Leupeptins / pharmacology
  • Molecular Sequence Data
  • NF-KappaB Inhibitor alpha
  • Proteasome Endopeptidase Complex / physiology*
  • Proteasome Inhibitors
  • Protein Structure, Tertiary / physiology
  • Tumor Necrosis Factor-alpha / pharmacology
  • Ubiquitin / metabolism*
  • Valosin Containing Protein

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • FAF1 protein, human
  • I-kappa B Proteins
  • Leupeptins
  • NFKBIA protein, human
  • Proteasome Inhibitors
  • Tumor Necrosis Factor-alpha
  • Ubiquitin
  • NF-KappaB Inhibitor alpha
  • Proteasome Endopeptidase Complex
  • Adenosine Triphosphatases
  • VCP protein, human
  • Valosin Containing Protein
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde