title: Human Fas-associated factor 1, interacting with ubiquitinated proteins and valosin-containing protein, is involved in the ubiquitin-proteasome pathway.
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.
authors.affiliation: Center for Cell Signaling Research, Division of Molecular Life Sciences and College of Pharmacy, Ewha Womans University, Seoul 120-750, South Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Song
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Yim
authors.forename: Eunhee
authors.initials: E
authors.lastname: Kim
authors.forename: Nam-Soon
authors.initials: NS
authors.lastname: Kim
authors.forename: Kong-Joo
authors.initials: KJ
authors.lastname: Lee
mesh_terms: 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
chemical_list: 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
references.citation: Nat Biotechnol. 2000 May;18(5):538-43
references.pmid: 10802622
references.citation: J Biol Chem. 2005 Mar 4;280(9):8125-33
references.pmid: 15596450
references.citation: J Mol Biol. 2001 Mar 16;307(1):17-24
references.pmid: 11243799
references.citation: Nature. 2001 Jul 19;412(6844):283, 285-6
references.pmid: 11460144
references.citation: J Mol Biol. 2001 Aug 10;311(2):255-63
references.pmid: 11478859
references.citation: Nat Cell Biol. 2001 Aug;3(8):740-4
references.pmid: 11483959
references.citation: Mol Cell. 2001 Sep;8(3):499-504
references.pmid: 11583613
references.citation: Nat Cell Biol. 2001 Oct;3(10):939-43
references.pmid: 11584278
references.citation: Nature. 2001 Dec 6;414(6864):652-6
references.pmid: 11740563
references.citation: Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):745-50
references.pmid: 11805328
references.citation: Curr Biol. 2002 Mar 5;12(5):R182-4
references.pmid: 11882310
references.citation: J Cell Biol. 2002 Apr 29;157(3):417-27
references.pmid: 11980917
references.citation: Curr Biol. 2002 May 14;12(10):R366-71
references.pmid: 12015140
references.citation: Mol Cell Biol. 2002 Jul;22(13):4902-13
references.pmid: 12052895
references.citation: J Mol Biol. 2002 Jun 21;319(5):1243-55
references.pmid: 12079361
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14374-9
references.pmid: 12391322
references.citation: EMBO J. 2002 Nov 1;21(21):5645-52
references.pmid: 12411482
references.citation: J Biol Chem. 2003 Mar 14;278(11):8951-9
references.pmid: 12643283
references.citation: FASEB J. 2003 May;17(8):790-9
references.pmid: 12724336
references.citation: J Biol Chem. 2003 Jun 27;278(26):24003-10
references.pmid: 12702723
references.citation: Nat Biotechnol. 2003 Aug;21(8):921-6
references.pmid: 12872131
references.citation: Mol Cell Biol. 2003 Sep;23(18):6469-83
references.pmid: 12944474
references.citation: Oncogene. 2003 Sep 1;22(37):5755-73
references.pmid: 12947384
references.citation: J Biol Chem. 2004 Jan 23;279(4):2544-9
references.pmid: 14600157
references.citation: J Biol Chem. 2004 Jun 25;279(26):26817-22
references.pmid: 15117949
references.citation: Cell. 2004 Jul 9;118(1):99-110
references.pmid: 15242647
references.citation: Genetics. 1982 Apr;100(4):547-63
references.pmid: 6749598
references.citation: J Biol Chem. 1995 Jul 21;270(29):17442-56
references.pmid: 7615550
references.citation: Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11894-8
references.pmid: 8524870
references.citation: J Biol Chem. 1996 Aug 23;271(34):20235-7
references.pmid: 8702753
references.citation: Trends Biochem Sci. 1996 May;21(5):172-3
references.pmid: 8871400
references.citation: EMBO J. 1996 Sep 16;15(18):4884-99
references.pmid: 8890162
references.citation: Nature. 1997 Jul 3;388(6637):75-8
references.pmid: 9214505
references.citation: FEBS Lett. 1997 Jul 21;412(1):102-6
references.pmid: 9257699
references.citation: J Biol Chem. 1998 Feb 6;273(6):3562-73
references.pmid: 9452483
references.citation: Cell. 1998 Mar 6;92(5):603-10
references.pmid: 9506515
references.citation: J Cell Sci. 1998 Aug;111 ( Pt 16):2353-63
references.pmid: 9683630
references.citation: Annu Rev Biochem. 1998;67:425-79
references.pmid: 9759494
references.citation: Nature. 1998 Dec 10;396(6711):590-4
references.pmid: 9859996
references.citation: Cell. 1999 Mar 5;96(5):635-44
references.pmid: 10089879
references.citation: Cell Death Differ. 1999 Apr;6(4):303-13
references.pmid: 10381632
references.citation: Biochem Biophys Res Commun. 1999 Aug 27;262(2):388-94
references.pmid: 10462485
references.citation: EMBO J. 2000 May 15;19(10):2181-92
references.pmid: 10811609