Identification of novel mitosis regulators through data mining with human centromere/kinetochore proteins as group queries

BMC Cell Biology

Song-Tao Liu²  Zhidong Gu¹  Shermeen Sufi²  Peter Oladimeji²  Kexi Wang²  Aaron R Tipton² 

[1] Ruijin Hospital, Shanghai, 200025, China;Department of Biological Sciences, University of Toledo, Toledo, OH, 43606, USA

关键词: Co-expression;    Protein-protein interaction;    Data mining;    Centrosome;    Kinetochore;    Centromere;   

Others  :  856972
DOI  :  10.1186/1471-2121-13-15

 received in 2012-02-13, accepted in 2012-06-19,  发布年份 2012

【 摘 要 】

Background

Proteins functioning in the same biological pathway tend to be transcriptionally co-regulated or form protein-protein interactions (PPI). Multiple spatially and temporally regulated events are coordinated during mitosis to achieve faithful chromosome segregation. The molecular players participating in mitosis regulation are still being unravelled experimentally or using in silico methods.

Results

An extensive literature review has led to a compilation of 196 human centromere/kinetochore proteins, all with experimental evidence supporting the subcellular localization. Sixty-four were designated as “core” centromere/kinetochore components based on peak expression and/or well-characterized functions during mitosis. By interrogating and integrating online resources, we have mined for genes/proteins that display transcriptional co-expression or PPI with the core centromere/kinetochore components. Top-ranked hubs in either co-expression or PPI network are not only enriched with known mitosis regulators, but also contain candidates whose mitotic functions are not yet established. Experimental validation found that KIAA1377 is a novel centrosomal protein that also associates with microtubules and midbody; while TRIP13 is a novel kinetochore protein and directly interacts with mitotic checkpoint silencing protein p31^comet.

Conclusions

Transcriptional co-expression and PPI network analyses with known human centromere/kinetochore proteins as a query group help identify novel potential mitosis regulators.

【 授权许可】

   
2012 Tipton et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Pines J, Rieder CL: Re-staging mitosis: a contemporary view of mitotic progression. Nature cell biology 2001, 3(1):E3-E6.
• [2]Muller GA, Engeland K: The central role of CDE/CHR promoter elements in the regulation of cell cycle-dependent gene transcription. FEBS J , 277(4):877-893.
• [3]Laoukili J, Kooistra MR, Bras A, Kauw J, Kerkhoven RM, Morrison A, Clevers H, Medema RH: FoxM1 is required for execution of the mitotic programme and chromosome stability. Nature cell biology 2005, 7(2):126-136.
• [4]Furuno N, den Elzen N, Pines J: Human cyclin A is required for mitosis until mid prophase. The Journal of cell biology 1999, 147(2):295-306.
• [5]Musacchio A, Salmon ED: The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol 2007, 8(5):379-393.
• [6]Potapova TA, Daum JR, Pittman BD, Hudson JR, Jones TN, Satinover DL, Stukenberg PT, Gorbsky GJ: The reversibility of mitotic exit in vertebrate cells. Nature 2006, 440(7086):954-958.
• [7]Cheeseman IM, Desai A: Molecular architecture of the kinetochore-microtubule interface. Nature reviews 2008, 9(1):33-46.
• [8]Chan GK, Liu ST, Yen TJ: Kinetochore structure and function. Trends Cell Biol 2005, 15(11):589-598.
• [9]Santaguida S, Musacchio A: The life and miracles of kinetochores. EMBO J 2009, 28(17):2511-2531.
• [10]Perpelescu M, Fukagawa T: The ABCs of CENPs. Chromosoma 2011, 120(5):425-446.
• [11]Amor DJ, Kalitsis P, Sumer H, Choo KH: Building the centromere: from foundation proteins to 3D organization. Trends Cell Biol 2004, 14(7):359-368.
• [12]Ohta S, Bukowski-Wills JC, Sanchez-Pulido L, Alves Fde L, Wood L, Chen ZA, Platani M, Fischer L, Hudson DF, Ponting CP, et al.: The protein composition of mitotic chromosomes determined using multiclassifier combinatorial proteomics. Cell 2010, 142(5):810-821.
• [13]Cusick ME, Klitgord N, Vidal M, Hill DE: Interactome: gateway into systems biology. Hum Mol Genet 2005, 14(Spec No. 2):R171-R181.
• [14]Rhodes DR, Chinnaiyan AM: Integrative analysis of the cancer transcriptome. Nat Genet 2005, 37(Suppl):S31-S37.
• [15]Eisen MB, Spellman PT, Brown PO, Botstein D: Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A 1998, 95(25):14863-14868.
• [16]Jablonski SA, Liu ST, Yen TJ: Targeting the kinetochore for mitosis-specific inhibitors. Cancer Biol Ther 2003, 2(3):236-241.
• [17]Meraldi P, McAinsh AD, Rheinbay E, Sorger PK: Phylogenetic and structural analysis of centromeric DNA and kinetochore proteins. Genome Biol 2006, 7(3):R23.
• [18]Gorbsky GJ, Ricketts WA: Differential expression of a phosphoepitope at the kinetochores of moving chromosomes. The Journal of cell biology 1993, 122(6):1311-1321.
• [19]Ahonen LJ, Kallio MJ, Daum JR, Bolton M, Manke IA, Yaffe MB, Stukenberg PT, Gorbsky GJ: Polo-like kinase 1 creates the tension-sensing 3 F3/2 phosphoepitope and modulates the association of spindle-checkpoint proteins at kinetochores. Curr Biol 2005, 15(12):1078-1089.
• [20]Wong OK, Fang G: Plx1 is the 3 F3/2 kinase responsible for targeting spindle checkpoint proteins to kinetochores. The Journal of cell biology 2005, 170(5):709-719.
• [21]Wong OK, Fang G: Cdk1 phosphorylation of BubR1 controls spindle checkpoint arrest and Plk1-mediated formation of the 3 F3/2 epitope. The Journal of cell biology 2007, 179(4):611-617.
• [22]Peters JM, Tedeschi A, Schmitz J: The cohesin complex and its roles in chromosome biology. Genes Dev 2008, 22(22):3089-3114.
• [23]Hirano T: Condensins: organizing and segregating the genome. Curr Biol 2005, 15(7):R265-R275.
• [24]Mishra RK, Chakraborty P, Arnaoutov A, Fontoura BM, Dasso M: The Nup107-160 complex and gamma-TuRC regulate microtubule polymerization at kinetochores. Nature cell biology , 12(2):164-169.
• [25]Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al.: Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 2000, 25(1):25-29.
• [26]Steensgaard P, Garre M, Muradore I, Transidico P, Nigg EA, Kitagawa K, Earnshaw WC, Faretta M, Musacchio A: Sgt1 is required for human kinetochore assembly. EMBO reports 2004, 5(6):626-631.
• [27]Mukhopadhyay D, Arnaoutov A, Dasso M: The SUMO protease SENP6 is essential for inner kinetochore assembly. The Journal of cell biology 2010, 188(5):681-692.
• [28]Zhang B, Horvath S: A general framework for weighted gene co-expression network analysis. Stat Appl Genet Mol Biol 2005, 4:Article17.
• [29]Benson M, Breitling R: Network theory to understand microarray studies of complex diseases. Curr Mol Med 2006, 6(6):695-701.
• [30]Lee HK, Hsu AK, Sajdak J, Qin J, Pavlidis P: Coexpression analysis of human genes across many microarray data sets. Genome Res 2004, 14(6):1085-1094.
• [31]Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A, Chinnaiyan AM: Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression. Proc Natl Acad Sci U S A 2004, 101(25):9309-9314.
• [32]Stuart JM, Segal E, Koller D, Kim SK: A gene-coexpression network for global discovery of conserved genetic modules. Science (New York, NY 2003 , 302(5643):249-255.
• [33]Zhang W, Morris QD, Chang R, Shai O, Bakowski MA, Mitsakakis N, Mohammad N, Robinson MD, Zirngibl R, Somogyi E, et al.: The functional landscape of mouse gene expression. J Biol 2004, 3(5):21.
• [34]Ruan J, Dean AK, Zhang W: A general co-expression network-based approach to gene expression analysis: comparison and applications. BMC Syst Biol , 4:8.
• [35]Mefford D, Mefford JA: Enumerating the gene sets in breast cancer, a "direct" alternative to hierarchical clustering. BMC Genomics , 11((1):482.
• [36]Starr DA, Saffery R, Li Z, Simpson AE, Choo KH, Yen TJ, Goldberg ML: HZwint-1, a novel human kinetochore component that interacts with HZW10. Journal of cell science 2000, 113(Pt 11):1939-1950.
• [37]Uhlmann F: A matter of choice: the establishment of sister chromatid cohesion. EMBO reports 2009, 10(10):1095-1102.
• [38]Kumar A, Girimaji SC, Duvvari MR, Blanton SH: Mutations in STIL, encoding a pericentriolar and centrosomal protein, cause primary microcephaly. Am J Hum Genet 2009, 84(2):286-290.
• [39]Maxwell CA, Keats JJ, Crainie M, Sun X, Yen T, Shibuya E, Hendzel M, Chan G, Pilarski LM: RHAMM is a centrosomal protein that interacts with dynein and maintains spindle pole stability. Molecular biology of the cell 2003, 14(6):2262-2276.
• [40]Lagana A, Dorn JF, De Rop V, Ladouceur AM, Maddox AS, Maddox PS: A small GTPase molecular switch regulates epigenetic centromere maintenance by stabilizing newly incorporated CENP-A. Nature cell biology 2010, 12(12):1186-1193.
• [41]Okada M, Okawa K, Isobe T, Fukagawa T: CENP-H-containing complex facilitates centromere deposition of CENP-A in cooperation with FACT and CHD1. Molecular biology of the cell 2009, 20(18):3986-3995.
• [42]Raemaekers T, Ribbeck K, Beaudouin J, Annaert W, Van Camp M, Stockmans I, Smets N, Bouillon R, Ellenberg J, Carmeliet G: NuSAP, a novel microtubule-associated protein involved in mitotic spindle organization. The Journal of cell biology 2003, 162(6):1017-1029.
• [43]Seki A, Fang G: CKAP2 is a spindle-associated protein degraded by APC/C-Cdh1 during mitotic exit. J Biol Chem 2007, 282(20):15103-15113.
• [44]Foltz DR, Jansen LE, Bailey AO, Yates JR, Bassett EA, Wood S, Black BE, Cleveland DW: Centromere-specific assembly of CENP-a nucleosomes is mediated by HJURP. Cell 2009, 137(3):472-484.
• [45]Foltz DR, Jansen LE, Black BE, Bailey AO, Yates JR, Cleveland DW: The human CENP-A centromeric nucleosome-associated complex. Nature cell biology 2006, 8(5):458-469.
• [46]Nayak T, Edgerton-Morgan H, Horio T, Xiong Y, De Souza CP, Osmani SA, Oakley BR: Gamma-tubulin regulates the anaphase-promoting complex/cyclosome during interphase. The Journal of cell biology , 190(3):317-330.
• [47]Prasanth SG, Prasanth KV, Stillman B: Orc6 involved in DNA replication, chromosome segregation, and cytokinesis. Science (New York, NY 2002, 297(5583):1026-1031.
• [48]Obayashi T, Kinoshita K: Rank of correlation coefficient as a comparable measure for biological significance of gene coexpression. DNA Res 2009, 16(5):249-260.
• [49]Obayashi T, Hayashi S, Shibaoka M, Saeki M, Ohta H, Kinoshita K: COXPRESdb: a database of coexpressed gene networks in mammals. Nucleic Acids Res 2008, 36(Database issue):D77-D82.
• [50]Chan KL, Palmai-Pallag T, Ying S, Hickson ID: Replication stress induces sister-chromatid bridging at fragile site loci in mitosis. Nature cell biology 2009, 11(6):753-760.
• [51]Dammermann A, Pemble H, Mitchell BJ, McLeod I, Yates JR, Kintner C, Desai AB, Oegema K: The hydrolethalus syndrome protein HYLS-1 links core centriole structure to cilia formation. Genes Dev 2009, 23(17):2046-2059.
• [52]Chen TC, Lee SA, Hong TM, Shih JY, Lai JM, Chiou HY, Yang SC, Chan CH, Kao CY, Yang PC, et al.: From midbody protein-protein interaction network construction to novel regulators in cytokinesis. Journal of proteome research 2009, 8(11):4943-4953.
• [53]Chen TC, Lee SA, Chan CH, Juang YL, Hong YR, Huang YH, Lai JM, Kao CY, Huang CY: Cliques in mitotic spindle network bring kinetochore-associated complexes to form dependence pathway. Proteomics 2009, 9(16):4048-4062.
• [54]Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, Watanabe Y: Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Nature 2006, 441(7089):46-52.
• [55]Foley EA, Maldonado M, Kapoor TM: Formation of stable attachments between kinetochores and microtubules depends on the B56-PP2A phosphatase. Nature cell biology 2011, 13(10):1265-1271.
• [56]Cayrol C, Cougoule C, Wright M: The beta2-adaptin clathrin adaptor interacts with the mitotic checkpoint kinase BubR1. Biochem Biophys Res Commun 2002, 298(5):720-730.
• [57]Royle SJ, Bright NA, Lagnado L: Clathrin is required for the function of the mitotic spindle. Nature 2005, 434(7037):1152-1157.
• [58]Lin CH, Hu CK, Shih HM: Clathrin heavy chain mediates TACC3 targeting to mitotic spindles to ensure spindle stability. The Journal of cell biology 2010, 189(7):1097-1105.
• [59]Nakanishi A, Han X, Saito H, Taguchi K, Ohta Y, Imajoh-Ohmi S, Miki Y: Interference with BRCA2, which localizes to the centrosome during S and early M phase, leads to abnormal nuclear division. Biochem Biophys Res Commun 2007, 355(1):34-40.
• [60]Deane CM, Salwinski L, Xenarios I, Eisenberg D: Protein interactions: two methods for assessment of the reliability of high throughput observations. Mol Cell Proteomics 2002, 1(5):349-356.
• [61]Bader JS, Chaudhuri A, Rothberg JM, Chant J: Gaining confidence in high-throughput protein interaction networks. Nat Biotechnol 2004, 22(1):78-85.
• [62]Draghici S, Khatri P, Eklund AC, Szallasi Z: Reliability and reproducibility issues in DNA microarray measurements. Trends Genet 2006, 22(2):101-109.
• [63]Li XC, Schimenti JC: Mouse pachytene checkpoint 2 (trip13) is required for completing meiotic recombination but not synapsis. PLoS Genet 2007, 3(8):e130.
• [64]Roig I, Dowdle JA, Toth A, de Rooij DG, Jasin M, Keeney S: Mouse TRIP13/PCH2 is required for recombination and normal higher-order chromosome structure during meiosis. PLoS Genet 2010, 6(8):.
• [65]Wojtasz L, Daniel K, Roig I, Bolcun-Filas E, Xu H, Boonsanay V, Eckmann CR, Cooke HJ, Jasin M, Keeney S, et al.: Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase. PLoS Genet 2009, 5(10):e1000702.
• [66]Habu T, Kim SH, Weinstein J, Matsumoto T: Identification of a MAD2-binding protein, CMT2, and its role in mitosis. EMBO J 2002, 21(23):6419-6428.
• [67]Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, et al.: Towards a proteome-scale map of the human protein-protein interaction network. Nature 2005, 437(7062):1173-1178.
• [68]Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, et al.: A human protein-protein interaction network: a resource for annotating the proteome. Cell 2005, 122(6):957-968.
• [69]Yasugi T, Vidal M, Sakai H, Howley PM, Benson JD: Two classes of human papillomavirus type 16 E1 mutants suggest pleiotropic conformational constraints affecting E1 multimerization, E2 interaction, and interaction with cellular proteins. J Virol 1997, 71(8):5942-5951.
• [70]Carter SL, Eklund AC, Kohane IS, Harris LN, Szallasi Z: A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers. Nat Genet 2006, 38(9):1043-1048.
• [71]Martin KJ, Patrick DR, Bissell MJ, Fournier MV: Prognostic breast cancer signature identified from 3D culture model accurately predicts clinical outcome across independent datasets. PLoS One 2008, 3(8):e2994.
• [72]Miniowitz-Shemtov S, Teichner A, Sitry-Shevah D, Hershko A: ATP is required for the release of the anaphase-promoting complex/cyclosome from inhibition by the mitotic checkpoint. Proc Natl Acad Sci U S A 2010, 107(12):5351-5356.
• [73]Teichner A, Eytan E, Sitry-Shevah D, Miniowitz-Shemtov S, Dumin E, Gromis J, Hershko A: p31comet promotes disassembly of the mitotic checkpoint complex in an ATP-dependent process. Proc Natl Acad Sci U S A 2011, 108(8):3187-3192.
• [74]Patterson KI, Brummer T, O'Brien PM, Daly RJ: Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochem J 2009, 418(3):475-489.
• [75]Abe Y, Takeuchi T, Kagawa-Miki L, Ueda N, Shigemoto K, Yasukawa M, Kito K: A mitotic kinase TOPK enhances Cdk1/cyclin B1-dependent phosphorylation of PRC1 and promotes cytokinesis. J Mol Biol 2007, 370(2):231-245.
• [76]Hannon GJ, Casso D, Beach D: KAP: a dual specificity phosphatase that interacts with cyclin-dependent kinases. Proc Natl Acad Sci U S A 1994, 91(5):1731-1735.
• [77]Poon RY, Hunter T: Dephosphorylation of Cdk2 Thr160 by the cyclin-dependent kinase-interacting phosphatase KAP in the absence of cyclin. Science (New York, NY 1995, 270(5233):90-93.
• [78]Song MH, Aravind L, Muller-Reichert T, O'Connell KF: The conserved protein SZY-20 opposes the Plk4-related kinase ZYG-1 to limit centrosome size. Developmental cell 2008, 15(6):901-912.
• [79]Alliegro MC, Alliegro MA: Centrosomal RNA correlates with intron-poor nuclear genes in Spisula oocytes. Proc Natl Acad Sci U S A 2008, 105(19):6993-6997.
• [80]Davezac N, Baldin V, Blot J, Ducommun B, Tassan JP: Human pEg3 kinase associates with and phosphorylates CDC25B phosphatase: a potential role for pEg3 in cell cycle regulation. Oncogene 2002, 21(50):7630-7641.
• [81]Le Page Y, Chartrain I, Badouel C, Tassan JP: A functional analysis of MELK in cell division reveals a transition in the mode of cytokinesis during Xenopus development. Journal of cell science 2011, 124(Pt 6):958-968.
• [82]Liao H, Winkfein RJ, Mack G, Rattner JB, Yen TJ: CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis. J Cell Biol 1995, 130:507-518.
• [83]Alibes A, Yankilevich P, Canada A, Diaz-Uriarte R: IDconverter and IDClight: conversion and annotation of gene and protein IDs. BMC Bioinforma 2007, 8:9.
• [84]Kent WJ, Hsu F, Karolchik D, Kuhn RM, Clawson H, Trumbower H, Haussler D: Exploring relationships and mining data with the UCSC Gene Sorter. Genome Res 2005, 15(5):737-741.
• [85]Su AI, Cooke MP, Ching KA, Hakak Y, Walker JR, Wiltshire T, Orth AP, Vega RG, Sapinoso LM, Moqrich A, et al.: Large-scale analysis of the human and mouse transcriptomes. Proc Natl Acad Sci U S A 2002, 99(7):4465-4470.
• [86]Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D, Zhang J, Soden R, Hayakawa M, Kreiman G, et al.: A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci U S A 2004, 101(16):6062-6067.
• [87]Lee SA, Chan CH, Chen TC, Yang CY, Huang KC, Tsai CH, Lai JM, Wang FS, Kao CY, Huang CY: POINeT: protein interactome with sub-network analysis and hub prioritization. BMC Bioinforma 2009, 10:114.
• [88]Tipton AR, Tipton M, Yen T, Liu ST: Closed MAD2 (C-MAD2) is selectively incorporated into the mitotic checkpoint complex (MCC). Cell cycle (Georgetown, Tex 2011, 10(21):3740-3750.
• [89]Tipton AR, Wang K, Link L, Bellizzi JJ, Huang H, Yen T, Liu ST: BUBR1 and Closed MAD2 (C-MAD2) Interact Directly to Assemble a Functional Mitotic Checkpoint Complex. J Biol Chem 2011, 286(24):21173-21179.
• [90]Liu ST, Hittle JC, Jablonski SA, Campbell MS, Yoda K, Yen TJ: Human CENP-I specifies localization of CENP-F, MAD1 and MAD2 to kinetochores and is essential for mitosis. Nature cell biology 2003, 5(4):341-345.