title: Proteomic analysis of the human cyclin-dependent kinase family reveals a novel CDK5 complex involved in cell growth and migration.
abstract: Cyclin-dependent kinases (CDKs) are the catalytic subunits of a family of mammalian heterodimeric serine/threonine kinases that play critical roles in the control of cell-cycle progression, transcription, and neuronal functions. However, the functions, substrates, and regulation of many CDKs are poorly understood. To systematically investigate these features of CDKs, we conducted a proteomic analysis of the CDK family and identified their associated protein complexes in two different cell lines using a modified SAINT (Significance Analysis of INTeractome) method. The mass spectrometry data were deposited to ProteomeXchange with identifier PXD000593 and DOI 10.6019/PXD000593. We identified 753 high-confidence candidate interaction proteins (HCIPs) in HEK293T cells and 352 HCIPs in MCF10A cells. We subsequently focused on a neuron-specific CDK, CDK5, and uncovered two novel CDK5-binding partners, KIAA0528 and fibroblast growth factor (acidic) intracellular binding protein (FIBP), in non-neuronal cells. We showed that these three proteins form a stable complex, with KIAA0528 and FIBP being required for the assembly and stability of the complex. Furthermore, CDK5-, KIAA0528-, or FIBP-depleted breast cancer cells displayed impaired proliferation and decreased migration, suggesting that this complex is required for cell growth and migration in non-neural cells. Our study uncovers new aspects of CDK functions, which provide direction for further investigation of these critical protein kinases.
authors.affiliation: From the ‡Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; §Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030.
authors.forename: Shuangbing
authors.initials: S
authors.lastname: Xu
authors.affiliation: §Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: §Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030.
authors.forename: Zihua
authors.initials: Z
authors.lastname: Gong
authors.affiliation: §Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Wang
authors.affiliation: §Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Li
authors.affiliation: §Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030.
authors.forename: Binoj Chandrasekharan
authors.initials: BC
authors.lastname: Nair
authors.affiliation: §Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030.
authors.forename: Hailong
authors.initials: H
authors.lastname: Piao
authors.affiliation: From the ‡Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China;
authors.forename: Kunyu
authors.initials: K
authors.lastname: Yang
authors.affiliation: From the ‡Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China;
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.affiliation: §Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 jchen8@mdanderson.org.
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
mesh_terms: D001943:Breast Neoplasms; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism*; D011485:Protein Binding; D060066:Protein Interaction Maps; D040901:Proteomics
chemical_list: D046912:Multiprotein Complexes; D005346:Fibroblast Growth Factors; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human
references.citation: Cancer Res. 2006 Aug 1;66(15):7509-15
references.pmid: 16885348
references.citation: Biochem Pharmacol. 2012 Oct 15;84(8):985-93
references.pmid: 22795893
references.citation: Annu Rev Cell Dev Biol. 2011;27:465-91
references.pmid: 21740229
references.citation: Neuron. 2000 Jun;26(3):633-46
references.pmid: 10896159
references.citation: Biochem J. 1998 Nov 15;336 ( Pt 1):213-22
references.pmid: 9806903
references.citation: Nat Cell Biol. 2009 Nov;11(11):1275-6
references.pmid: 19884882
references.citation: Nature. 1994 Sep 29;371(6496):423-6
references.pmid: 8090222
references.citation: Trends Biochem Sci. 2005 Nov;30(11):630-41
references.pmid: 16236519
references.citation: Cell. 1992 Oct 30;71(3):505-14
references.pmid: 1358458
references.citation: Bioinformatics. 2011 Feb 1;27(3):431-2
references.pmid: 21149340
references.citation: Neuroreport. 1995 May 30;6(8):1130-2
references.pmid: 7662893
references.citation: Cell Cycle. 2010 Jan 15;9(2):284-311
references.pmid: 20061803
references.citation: EMBO J. 2005 Apr 6;24(7):1465-76
references.pmid: 15775963
references.citation: Nat Methods. 2007 Mar;4(3):207-14
references.pmid: 17327847
references.citation: Clin Cancer Res. 2011 Oct 1;17(19):6140-50
references.pmid: 21825040
references.citation: Nat Rev Cancer. 2009 Mar;9(3):153-66
references.pmid: 19238148
references.citation: Oncogene. 2008 Jul 31;27(33):4615-24
references.pmid: 18391978
references.citation: Nucleic Acids Res. 2013 Jan;41(Database issue):D1063-9
references.pmid: 23203882
references.citation: Mol Biol Cell. 2013 Aug;24(16):2544-57
references.pmid: 23804653
references.citation: Mol Cell Biol. 2008 Oct;28(19):5924-36
references.pmid: 18663000
references.citation: J Clin Invest. 2009 Oct;119(10):3089-101
references.pmid: 19729834
references.citation: Nat Biotechnol. 2014 Mar;32(3):223-6
references.pmid: 24727771
references.citation: Biochim Biophys Acta. 2002 Mar 19;1574(2):157-63
references.pmid: 11955625
references.citation: Mol Cell Proteomics. 2012 Dec;11(12):1682-9
references.pmid: 22949509
references.citation: J Neurochem. 1998 Jan;70(1):335-40
references.pmid: 9422379
references.citation: Nat Methods. 2013 Apr;10(4):307-14
references.pmid: 23455922
references.citation: J Biol Chem. 2011 Feb 11;286(6):4364-70
references.pmid: 21187284
references.citation: Nucleic Acids Res. 2013 Jan;41(Database issue):D816-23
references.pmid: 23203989
references.citation: Nat Med. 2012 Oct;18(10):1511-7
references.pmid: 23001183
references.citation: Cell Signal. 2011 Nov;23(11):1698-707
references.pmid: 21741478
references.citation: Genes Dev. 2012 Sep 1;26(17):1959-71
references.pmid: 22948661
references.citation: Mol Cell Proteomics. 2014 Jan;13(1):119-31
references.pmid: 24126142
references.citation: Nat Methods. 2013 Aug;10(8):730-6
references.pmid: 23921808
references.citation: J Biol Chem. 2007 Feb 2;282(5):2776-84
references.pmid: 17145757
references.citation: Mol Cell Proteomics. 2008 Dec;7(12):2373-85
references.pmid: 18644780
references.citation: Bioessays. 2006 Oct;28(10):1023-34
references.pmid: 16998837
references.citation: Nature. 1994 Sep 29;371(6496):419-23
references.pmid: 8090221
references.citation: Science. 2010 May 21;328(5981):1043-6
references.pmid: 20489023
references.citation: Biochem J. 2000 Dec 15;352 Pt 3:629-35
references.pmid: 11104667
references.citation: J Biol Chem. 2011 Sep 23;286(38):33141-9
references.pmid: 21799006
references.citation: Nucleic Acids Res. 2009 Nov;37(21):7151-62
references.pmid: 19786495
references.citation: Mol Cell Biol. 2006 Apr;26(7):2736-45
references.pmid: 16537916
references.citation: Anal Chem. 1996 Mar 1;68(5):850-8
references.pmid: 8779443
references.citation: Cancer Res. 2006 May 1;66(9):4826-34
references.pmid: 16651438
references.citation: Physiol Rev. 2011 Jul;91(3):973-1007
references.pmid: 21742793
references.citation: Proc Natl Acad Sci U S A. 2008 May 27;105(21):7570-5
references.pmid: 18487454
references.citation: J Biol Chem. 2013 Feb 1;288(5):3174-83
references.pmid: 23229552
references.citation: Cell Metab. 2011 Sep 7;14(3):378-89
references.pmid: 21907143
references.citation: Cell Signal. 2012 Jan;24(1):44-52
references.pmid: 21924349
references.citation: J Hum Genet. 2009 May;54(5):298-303
references.pmid: 19343042
references.citation: Physiol Genomics. 2008 Apr 22;33(2):193-204
references.pmid: 18285519
references.citation: Cancer Res. 2010 Jun 1;70(11):4460-9
references.pmid: 20484029
references.citation: Nat Methods. 2012 Nov;9(11):1069-76
references.pmid: 23132118
references.citation: Curr Opin Genet Dev. 2007 Feb;17(1):60-5
references.pmid: 17208431
references.citation: Dev Cell. 2011 Oct 18;21(4):655-68
references.pmid: 21944720
references.citation: Oncogene. 2009 Aug 20;28(33):2925-39
references.pmid: 19561645
references.citation: Annu Rev Cell Dev Biol. 1997;13:261-91
references.pmid: 9442875
references.citation: Mol Cell. 2004 Jun 4;14(5):685-91
references.pmid: 15175163
references.citation: Cell Mol Neurobiol. 2008 May;28(3):351-69
references.pmid: 18183483
references.citation: Prog Neurobiol. 2011 Jun;94(1):49-63
references.pmid: 21473899
references.citation: Biochem Biophys Res Commun. 2007 Mar 16;354(3):735-40
references.pmid: 17261272
references.citation: Int J Oncol. 2006 Jan;28(1):191-4
references.pmid: 16327995
references.citation: Nat Methods. 2011 Jan;8(1):70-3
references.pmid: 21131968
references.citation: Expert Opin Ther Targets. 2010 Nov;14(11):1199-212
references.pmid: 20932174