title: Mechanisms and function of substrate recruitment by F-box proteins.
abstract: S phase kinase-associated protein 1 (SKP1)-cullin 1 (CUL1)-F-box protein (SCF) ubiquitin ligase complexes use a family of F-box proteins as substrate adaptors to mediate the degradation of a large number of regulatory proteins involved in diverse processes. The dysregulation of SCF complexes and their substrates contributes to multiple pathologies. In the 14 years since the identification and annotation of the F-box protein family, the continued identification and characterization of novel substrates has greatly expanded our knowledge of the regulation of substrate targeting and the roles of F-box proteins in biological processes. Here, we focus on the evolution of our understanding of substrate recruitment by F-box proteins, the dysregulation of substrate recruitment in disease and potential avenues for F-box protein-directed disease therapies.
authors: Department of Pathology, New York University Cancer Institute, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, New York 10016, USA. skaarlab@gmail.com
authors: Jeffrey R
authors: JR
authors: Skaar
authors: Julia K
authors: JK
authors: Pagan
authors: Michele
authors: M
authors: Pagano
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D006801:Humans; D059748:Proteolysis; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics* / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics* / Q000378:metabolism*; D013379:Substrate Specificity / Q000502:physiology
chemical_list: D044786:S-Phase Kinase-Associated Proteins; C097351:SKP1 protein, human; D044843:SKP Cullin F-Box Protein Ligases
references: Mol Cell. 2013 Mar 28;49(6):1147-58
references: 23478445
references: J Biol Chem. 2012 Jul 6;287(28):23710-7
references: 22648410
references: Nat Cell Biol. 2013 May;15(5):472-80
references: 23604317
references: Mol Cell. 2012 Nov 30;48(4):572-86
references: 23063525
references: Nat Rev Genet. 2008 Oct;9(10):764-75
references: 18802415
references: J Biol Chem. 2010 Jun 25;285(26):20109-16
references: 20427287
references: Dev Cell. 2010 Feb 16;18(2):214-25
references: 20159592
references: PLoS One. 2012;7(6):e38263
references: 22719873
references: Cell. 2013 Mar 28;153(1):206-15
references: 23453757
references: Nature. 2010 Nov 18;468(7322):400-5
references: 20927106
references: Science. 2004 Oct 8;306(5694):269-71
references: 15472075
references: Oncogene. 2003 Nov 6;22(50):8063-71
references: 14603247
references: J Biol Chem. 2001 May 11;276(19):15920-8
references: 11278695
references: Nat Genet. 2012 Dec;44(12):1316-20
references: 23143595
references: Cell. 2007 Sep 7;130(5):943-57
references: 17803915
references: Genes Dev. 2006 Oct 1;20(19):2660-72
references: 16983144
references: Cancer Cell. 2007 Aug;12(2):131-44
references: 17692805
references: Nature. 2002 Jul 25;418(6896):438-42
references: 12140560
references: Cell. 2007 Jun 1;129(5):1011-23
references: 17462724
references: Neurology. 2009 Jan 20;72(3):240-5
references: 19038853
references: Science. 2011 Aug 26;333(6046):1157-60
references: 21798893
references: J Biol Chem. 2000 Jan 28;275(4):2877-84
references: 10644755
references: Dev Cell. 2009 Jul;17(1):9-26
references: 19619488
references: Nature. 2011 Mar 3;471(7336):110-4
references: 21368834
references: Mol Cell. 2005 May 13;18(4):425-34
references: 15893726
references: Mol Cell. 2012 Apr 13;46(1):67-78
references: 22405651
references: Science. 2008 Nov 7;322(5903):923-9
references: 18988848
references: Mol Cell. 2003 Aug;12(2):381-92
references: 14536078
references: PLoS Pathog. 2009 Dec;5(12):e1000704
references: 20041211
references: Nat Commun. 2013;4:1642
references: 23535663
references: Mol Cell. 2011 Oct 21;44(2):317-24
references: 22017877
references: Nature. 2004 Mar 11;428(6979):190-3
references: 15014502
references: Chembiochem. 2012 Apr 16;13(6):788-91
references: 22492618
references: J Cell Sci. 2010 Jul 1;123(Pt 13):2163-9
references: 20516151
references: Cell Div. 2007 Feb 13;2:7
references: 17298674
references: Nature. 2010 Aug 12;466(7308):869-73
references: 20668451
references: Annu Rev Biochem. 2012;81:203-29
references: 22524316
references: J Exp Med. 2007 Aug 6;204(8):1825-35
references: 17646408
references: J Biol Chem. 2010 Apr 30;285(18):13896-906
references: 20181953
references: Science. 2012 Aug 31;337(6098):1094-7
references: 22798407
references: J Exp Med. 2007 Nov 26;204(12):2875-88
references: 17984302
references: Nat Rev Mol Cell Biol. 2008 Sep;9(9):679-90
references: 18698327
references: Immunol Rev. 2012 May;247(1):172-83
references: 22500840
references: Dev Cell. 2003 Jun;4(6):813-26
references: 12791267
references: Science. 2001 Feb 9;291(5506):1040-3
references: 11232563
references: J Biol Chem. 2012 May 11;287(20):16199-208
references: 22453922
references: Annu Rev Biochem. 2005;74:115-28
references: 15952883
references: J Biol Chem. 2003 Oct 31;278(44):43877-84
references: 12939278
references: EMBO Rep. 2008 Jun;9(6):536-42
references: 18516089
references: Nat Genet. 2010 Feb;42(2):105-16
references: 20081858
references: Chem Biol. 2012 Dec 21;19(12):1515-24
references: 23261596
references: Nat Cell Biol. 1999 Aug;1(4):207-14
references: 10559918
references: Cell. 2009 Jun 26;137(7):1358, 1358.e1
references: 19563764
references: Mol Cell. 2012 Oct 26;48(2):288-97
references: 23000173
references: Nature. 2001 Nov 29;414(6863):514-21
references: 11734846
references: Curr Biol. 2009 Jan 13;19(1):43-9
references: 19084407
references: Curr HIV Res. 2012 Jun;10(4):327-33
references: 22524181
references: Science. 2007 May 11;316(5826):897-900
references: 17463252
references: Science. 2009 Oct 30;326(5953):722-6
references: 19762597
references: Annu Rev Plant Biol. 2011;62:335-64
references: 21526969
references: J Biol Chem. 2008 May 9;283(19):12717-29
references: 18203720
references: Cell. 2013 Feb 28;152(5):1091-105
references: 23452855
references: Cell. 2007 Jun 15;129(6):1165-76
references: 17574027
references: Nature. 2010 Jul 1;466(7302):138-42
references: 20596027
references: Nat Cell Biol. 2001 Mar;3(3):321-4
references: 11231585
references: Curr Biol. 1999 Oct 21;9(20):1177-9
references: 10531035
references: Cell. 2005 Jul 15;122(1):45-57
references: 16009132
references: Nat Cell Biol. 2011 Jul 03;13(8):1004-9
references: 21725316
references: Cell. 2002 Mar 22;108(6):837-47
references: 11955436
references: Nature. 2013 Apr 4;496(7443):64-8
references: 23503662
references: Mol Cell. 2010 Dec 22;40(6):954-64
references: 21172660
references: Curr Opin Struct Biol. 2010 Dec;20(6):714-21
references: 20880695
references: Virology. 2011 Feb 5;410(1):119-28
references: 21106215
references: Nature. 2011 Sep 11;478(7367):64-9
references: 21909114
references: Cancer Res. 2007 Oct 1;67(19):9006-12
references: 17909001
references: Nat Cell Biol. 1999 Aug;1(4):193-9
references: 10559916
references: Mol Cell. 2005 Oct 7;20(1):9-19
references: 16209941
references: PLoS One. 2008;3(10):e3530
references: 18953409
references: Nat Rev Cancer. 2008 Feb;8(2):83-93
references: 18094723
references: Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8554-9
references: 11438690
references: Nature. 2012 Jan 5;481(7379):90-3
references: 22113614
references: Nat Commun. 2013;4:1641
references: 23535662
references: Nat Biotechnol. 2010 Jul;28(7):733-7
references: 20581844
references: J Biol Chem. 2005 Jul 22;280(29):26863-72
references: 15917222
references: Biochem Soc Trans. 2010 Feb;38(Pt 1):65-71
references: 20074037
references: Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3287-92
references: 22328159
references: Nat Biotechnol. 2010 Jul;28(7):738-42
references: 20581845
references: Oncogene. 2010 Sep 2;29(35):4865-73
references: 20543859
references: Am J Pathol. 2007 May;170(5):1793-805
references: 17456782
references: Nat Methods. 2009 Dec;6(12):917-22
references: 19915560
references: Front Biosci (Landmark Ed). 2012 Jun 01;17:2197-212
references: 22652772
references: Cancer Cell. 2005 Jul;8(1):25-33
references: 16023596
references: FEBS Lett. 2009 Feb 18;583(4):607-14
references: 19174161
references: Cell. 2009 May 29;137(5):873-86
references: 19446321
references: J Biol Chem. 2011 Apr 8;286(14):12766-74
references: 21324900
references: Science. 2007 May 11;316(5826):900-4
references: 17463251
references: Mol Cell. 2009 Aug 28;35(4):442-53
references: 19716789
references: J Biol Chem. 2003 Feb 14;278(7):4699-704
references: 12468532
references: J Exp Med. 2001 Nov 5;194(9):1299-311
references: 11696595
references: Science. 2008 Nov 7;322(5903):918-23
references: 18988847
references: Nature. 2011 Mar 3;471(7336):104-9
references: 21368833
references: Nat Cell Biol. 2012 Mar 04;14(4):375-85
references: 22388891
references: Curr Biol. 1999 Oct 21;9(20):1180-2
references: 10531037
references: Mol Cell. 2011 Oct 21;44(2):290-303
references: 22017875
references: Cell. 2013 Feb 28;152(5):1106-18
references: 23452856
references: J Pharmacol Exp Ther. 2009 Aug;330(2):430-9
references: 19458106
references: Science. 2009 Oct 30;326(5953):718-21
references: 19762596
references: Mol Cell. 2013 Mar 28;49(6):1159-66
references: 23478441
references: Nature. 2011 Oct 12;480(7375):128-31
references: 21993622
references: Nature. 2004 Mar 11;428(6979):194-8
references: 15014503
references: Nature. 2007 Apr 5;446(7136):640-5
references: 17410169
references: Mol Cell Proteomics. 2003 Dec;2(12):1350-8
references: 14525958
references: Cell. 2007 Dec 28;131(7):1248-59
references: 18160036
references: EMBO J. 1994 Dec 15;13(24):6087-98
references: 7813445
references: Nat Rev Cancer. 2008 Jun;8(6):438-49
references: 18500245
references: Mol Cell Biol. 2000 Apr;20(7):2423-35
references: 10713166
references: Mol Cell. 2007 Apr 13;26(1):131-43
references: 17434132
references: Nature. 2007 Jun 21;447(7147):966-71
references: 17515920
references: Am J Med Genet B Neuropsychiatr Genet. 2008 Oct 5;147B(7):1231-7
references: 18404645
references: Cancer Cell. 2007 Aug;12(2):115-30
references: 17692804
references: Nat Rev Mol Cell Biol. 2005 Jan;6(1):9-20
references: 15688063
references: Blood. 2000 Mar 15;95(6):2104-10
references: 10706881
references: J Biol Chem. 2009 Oct 9;284(41):27766-27779
references: 19679664
references: Nat Med. 2010 Oct;16(10):1152-6
references: 20852621
references: Proc Natl Acad Sci U S A. 2004 May 25;101(21):7937-42
references: 15148369
references: Nature. 2009 Jun 4;459(7247):722-5
references: 19412162
references: Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15240-5
references: 20696890
references: Blood. 2011 Nov 24;118(22):e168-79
references: 21940823
references: Nat Cell Biol. 2013 Jan;15(1):72-81
references: 23263282
references: Mol Cell. 2011 Oct 21;44(2):304-16
references: 22017876
references: Cancer Sci. 2013 Apr;104(4):508-15
references: 23305207
references: Cell. 2012 May 25;149(5):1023-34
references: 22632967
references: Annu Rev Biochem. 1998;67:425-79
references: 9759494
references: Genes Dev. 2004 Nov 1;18(21):2573-80
references: 15520277
references: Mol Cell. 2001 Mar;7(3):639-50
references: 11463388
references: Mol Cell. 2012 Aug 10;47(3):371-82
references: 22748924
references: Mol Cell. 2006 Nov 3;24(3):355-66
references: 17081987