Identification of genes periodically expressed in the human cell cycle and their expression in tumors.

The genome-wide program of gene expression during the cell division cycle in a human cancer cell line (HeLa) was characterized using cDNA microarrays. Transcripts of >850 genes showed periodic variation during the cell cycle. Hierarchical clustering of the expression patterns revealed coexpressed groups of previously well-characterized genes involved in essential cell cycle processes such as DNA replication, chromosome segregation, and cell adhesion along with genes of uncharacterized function. Most of the genes whose expression had previously been reported to correlate with the proliferative state of tumors were found herein also to be periodically expressed during the HeLa cell cycle. However, some of the genes periodically expressed in the HeLa cell cycle do not have a consistent correlation with tumor proliferation. Cell cycle-regulated transcripts of genes involved in fundamental processes such as DNA replication and chromosome segregation seem to be more highly expressed in proliferative tumors simply because they contain more cycling cells. The data in this report provide a comprehensive catalog of cell cycle regulated genes that can serve as a starting point for functional discovery. The full dataset is available at http://genome-www.stanford.edu/Human-CellCycle/HeLa/.

[1]  T. Puck,et al.  CLONAL GROWTH OF MAMMALIAN CELLS IN VITRO , 1956, The Journal of experimental medicine.

[2]  T. Puck,et al.  Clonal growth of mammalian cells in vitro; growth characteristics of colonies from single HeLa cells with and without a feeder layer. , 1956 .

[3]  E. Greenwald CHAPTER I – PHARMACOLOGY OF CANCER CHEMOTHERAPY , 1967 .

[4]  W. Dewey,et al.  Use of the mitotic selection procedure for cell cycle analysis. Comparison between the X-ray and cycloheximide G2 markers. , 1972, Experimental cell research.

[5]  W. Dewey,et al.  Use of the mitotic selection procedure for cell cycle analysis: emphasis on radiation-induced mitotic delay. , 1975, Methods in cell biology.

[6]  J. Mullins,et al.  Production of large numbers of mitotic mammalian cells by use of the reversible microtubule inhibitor nocodazole. Nocodazole accumulated mitotic cells. , 1980, Experimental cell research.

[7]  B. Jockusch,et al.  Interaction of alpha-actinin and vinculin with actin: opposite effects on filament network formation. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[8]  V. Devita,et al.  Cancer : Principles and Practice of Oncology , 1982 .

[9]  K. Adolph,et al.  Role of non-histones in chromosome structure. Cell cycle variations in protein synthesis. , 1982, The Journal of biological chemistry.

[10]  C. Der,et al.  Transforming genes of human bladder and lung carcinoma cell lines are homologous to the ras genes of Harvey and Kirsten sarcoma viruses. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Shin Lin,et al.  High-affinity interaction of vinculin with actin filaments in vitro , 1982, Cell.

[12]  J. Davies,et al.  Molecular Biology of the Cell , 1983, Bristol Medico-Chirurgical Journal.

[13]  G. Steele,et al.  Cancer: Principles and Practice of Oncology , 1983 .

[14]  G. Stein,et al.  Coordinate regulation of multiple histone mRNAs during the cell cycle in HeLa cells. , 1983, Nucleic acids research.

[15]  N. Heintz,et al.  Regulation of human histone gene expression: kinetics of accumulation and changes in the rate of synthesis and in the half-lives of individual histone mRNAs during the HeLa cell cycle , 1983, Molecular and cellular biology.

[16]  L. Kedes,et al.  Structure of a human histone cDNA: evidence that basally expressed histone genes have intervening sequences and encode polyadenylylated mRNAs. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[17]  L. Kaczmarek Protooncogene expression during the cell cycle. , 1986, Laboratory investigation; a journal of technical methods and pathology.

[18]  P. Nurse,et al.  Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2 , 1987, Nature.

[19]  W. Marzluff,et al.  Multiple regulatory steps control histone mRNA concentrations. , 1988, Trends in biochemical sciences.

[20]  D. Schümperli Multilevel regulation of replication-dependent histone genes. , 1988, Trends in genetics : TIG.

[21]  H. Crissman,et al.  Synchronization of human diploid fibroblasts at multiple stages of the cell cycle. , 1988, Experimental cell research.

[22]  Tony Hunter,et al.  Isolation of a human cyclin cDNA: Evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2 , 1989, Cell.

[23]  D. Cleveland Gene regulation through messenger RNA stability. , 1989, Current opinion in cell biology.

[24]  M. Mathews,et al.  Regulation of proliferating cell nuclear antigen during the cell cycle. , 1989, The Journal of biological chemistry.

[25]  Tony Hunter,et al.  Human cyclin A is adenovirus E1A-associated protein p60 and behaves differently from cyclin B , 1990, Nature.

[26]  P. Russell,et al.  Human cDNAs encoding homologs of the small p34Cdc28/Cdc2-associated protein of Saccharomyces cerevisiae and Schizosaccharomyces pombe. , 1990, Genes & development.

[27]  M. Barbacid,et al.  ras oncogenes: their role in neoplasia , 1990, European journal of clinical investigation.

[28]  B. Tribukait,et al.  S-phase-specific expression of mammalian ribonucleotide reductase R1 and R2 subunit mRNAs. , 1990, Biochemistry.

[29]  S. Reed,et al.  Isolation of three novel human cyclins by rescue of G1 cyclin (cln) function in yeast , 1991, Cell.

[30]  J. Bishop Molecular themes in oncogenesis , 1991, Cell.

[31]  K. Münger,et al.  The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[32]  D. Schümperli,et al.  Regulation of histone mRNA in the unperturbed cell cycle: evidence suggesting control at two posttranscriptional steps , 1991, Molecular and cellular biology.

[33]  W. Marzluff Histone 3' ends: essential and regulatory functions. , 1992, Gene expression.

[34]  S. Dalton,et al.  Cell cycle regulation of the human cdc2 gene. , 1992, The EMBO journal.

[35]  B. Geiger,et al.  Suppression of tumorigenicity in transformed cells after transfection with vinculin cDNA , 1992, The Journal of cell biology.

[36]  Marzluff Wf Histone 3' ends: essential and regulatory functions. , 1992 .

[37]  Roger Brent,et al.  C dil, a Human Gl and S Phase Protein Phosphatase That Associates with Cdk2 , 2003 .

[38]  J. Freeman,et al.  Cell cycle regulated expression of nucleolar antigen P120 in normal and transformed human fibroblasts , 1993, Journal of cellular physiology.

[39]  P. Yaswen,et al.  Blockage of EGF receptor signal transduction causes reversible arrest of normal and immortal human mammary epithelial cells with synchronous reentry into the cell cycle. , 1993, Experimental cell research.

[40]  S. Elledge,et al.  Human cyclin F. , 1994, The EMBO journal.

[41]  T. Karn,et al.  Induction and down-regulation of PLK, a human serine/threonine kinase expressed in proliferating cells and tumors. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[42]  David O. Morgan,et al.  A novel cyclin associates with M015/CDK7 to form the CDK-activating kinase , 1994, Cell.

[43]  J. Bartek,et al.  Cell cycle analysis of the activity, subcellular localization, and subunit composition of human CAK (CDK-activating kinase) , 1994, The Journal of cell biology.

[44]  D. Morgan,et al.  Activation of cyclin-dependent kinase 4 (cdk4) by mouse MO15-associated kinase , 1994, Molecular and cellular biology.

[45]  H Nojima,et al.  Cdc25A is a novel phosphatase functioning early in the cell cycle. , 1994, The EMBO journal.

[46]  J. Weinstein,et al.  A novel mammalian protein, p55CDC, present in dividing cells is associated with protein kinase activity and has homology to the Saccharomyces cerevisiae cell division cycle proteins Cdc20 and Cdc4 , 1994, Molecular and cellular biology.

[47]  J. Downing,et al.  Molecular cloning, expression pattern, and chromosomal localization of human CDKN2D/INK4d, an inhibitor of cyclin D-dependent kinases. , 1995, Genomics.

[48]  C. Der,et al.  Tyrosine phosphorylation regulates the adhesions of ras-transformed breast epithelia , 1995, The Journal of cell biology.

[49]  J. B. Rattner,et al.  CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis , 1995, The Journal of cell biology.

[50]  F. C. Lucibello,et al.  Periodic cdc25C transcription is mediated by a novel cell cycle‐regulated repressor element (CDE). , 1995, The EMBO journal.

[51]  J. Pines,et al.  Human cyclins B1 and B2 are localized to strikingly different structures: B1 to microtubules, B2 primarily to the Golgi apparatus. , 1995, The EMBO journal.

[52]  M. Roussel,et al.  Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6 , 1995, Molecular and cellular biology.

[53]  R. Erikson,et al.  Plk is an M-phase-specific protein kinase and interacts with a kinesin-like protein, CHO1/MKLP-1 , 1995, Molecular and cellular biology.

[54]  R. Weinberg,et al.  E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[55]  F. Solomon,et al.  Suppression of a conditional mutation in alpha-tubulin by overexpression of two checkpoint genes. , 1995, Journal of cell science.

[56]  R. Fotedar,et al.  Cell cycle control of DNA replication. , 1995, Progress in cell cycle research.

[57]  J. Nevins,et al.  Regulation of the cyclin E gene by transcription factor E2F1. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[58]  F. C. Lucibello,et al.  Cell cycle regulation of the cyclin A, cdc25C and cdc2 genes is based on a common mechanism of transcriptional repression. , 1995, The EMBO journal.

[59]  M. Stoehr,et al.  A critical appraisal of synchronization methods applied to achieve maximal enrichment of HeLa cells in specific cell cycle phases. , 1995, Experimental cell research.

[60]  C. Hunt,et al.  The cell cycle-coupled expression of topoisomerase IIalpha during S phase is regulated by mRNA stability and is disrupted by heat shock or ionizing radiation , 1996, Molecular and cellular biology.

[61]  K. Tanaka,et al.  Molecular cloning and characterization of human non-smooth muscle calponin. , 1996, Journal of biochemistry.

[62]  O. Tsolas,et al.  Selective interaction between parathymosin and histone H1. , 1996, European journal of biochemistry.

[63]  A. Berchuck,et al.  Cell cycle control of BRCA2. , 1996, Cancer research.

[64]  G. Crabtree,et al.  Diversity and specialization of mammalian SWI/SNF complexes. , 1996, Genes & development.

[65]  M. Whitfield,et al.  The protein that binds the 3' end of histone mRNA: a novel RNA-binding protein required for histone pre-mRNA processing. , 1996, Genes & development.

[66]  C. Boland,et al.  Expression of human MutS homolog 2 (hMSH2) protein in resting and proliferating cells. , 1996, Oncogene.

[67]  P. Farnham,et al.  Transcriptional regulation of the dihydrofolate reductase gene , 1996, BioEssays : news and reviews in molecular, cellular and developmental biology.

[68]  H. Lane,et al.  Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes , 1996, The Journal of cell biology.

[69]  M. Horne,et al.  Cyclin G1 and Cyclin G2 Comprise a New Family of Cyclins with Contrasting Tissue-specific and Cell Cycle-regulated Expression (*) , 1996, The Journal of Biological Chemistry.

[70]  L. Chodosh,et al.  Brca2 is coordinately regulated with Brca1 during proliferation and differentiation in mammary epithelial cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[71]  L. Goldstein,et al.  CENP-E Is a Plus End–Directed Kinetochore Motor Required for Metaphase Chromosome Alignment , 1997, Cell.

[72]  S. Melmed,et al.  Isolation and characterization of a pituitary tumor-transforming gene (PTTG). , 1997, Molecular endocrinology.

[73]  T. Hunter Oncoprotein Networks , 1997, Cell.

[74]  J Weinstein,et al.  Cell Cycle-regulated Expression, Phosphorylation, and Degradation of p55Cdc , 1997, The Journal of Biological Chemistry.

[75]  M. Kinch,et al.  Rho-stimulated contractility contributes to the fibroblastic phenotype of Ras-transformed epithelial cells. , 1997, Molecular biology of the cell.

[76]  D. Longo,et al.  Malignant transformation of mammalian cells initiated by constitutive expression of the polo-like kinase. , 1997, Biochemical and biophysical research communications.

[77]  K. Sullivan,et al.  Assembly of CENP-A into Centromeric Chromatin Requires a Cooperative Array of Nucleosomal DNA Contact Sites , 1997, The Journal of cell biology.

[78]  Jinhe Li,et al.  Alzheimer Presenilins in the Nuclear Membrane, Interphase Kinetochores, and Centrosomes Suggest a Role in Chromosome Segregation , 1997, Cell.

[79]  K. Kaibuchi,et al.  The Ras Target AF-6 Interacts with ZO-1 and Serves as a Peripheral Component of Tight Junctions in Epithelial Cells , 1997, The Journal of cell biology.

[80]  S. Kotani,et al.  Cell Cycle-dependent Expression and Spindle Pole Localization of a Novel Human Protein Kinase, Aik, Related to Aurora of Drosophila and Yeast Ipl1* , 1997, The Journal of Biological Chemistry.

[81]  M. Rüdiger Vinculin and α‐catenin: shared and unique functions in adherens junctions , 1998 .

[82]  M. Hurt,et al.  Role for a YY1-Binding Element in Replication-Dependent Mouse Histone Gene Expression , 1998, Molecular and Cellular Biology.

[83]  S. Weremowicz,et al.  The Human Homolog of Saccharomyces cerevisiae CDC45 * , 1998, The Journal of Biological Chemistry.

[84]  J. Nevins,et al.  E2F3 activity is regulated during the cell cycle and is required for the induction of S phase. , 1998, Genes & development.

[85]  Jian Kuang,et al.  Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation , 1998, Nature Genetics.

[86]  Ronald W. Davis,et al.  A genome-wide transcriptional analysis of the mitotic cell cycle. , 1998, Molecular cell.

[87]  G. Williams,et al.  Improved cervical smear assessment using antibodies against proteins that regulate DNA replication. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[88]  N. Copeland,et al.  cDNA cloning, expression, subcellular localization, and chromosomal assignment of mammalian aurora homologues, aurora-related kinase (ARK) 1 and 2. , 1998, Biochemical and biophysical research communications.

[89]  K. Kinzler,et al.  Genetic instabilities in human cancers , 1998, Nature.

[90]  J. Nevins,et al.  Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[91]  Jidong Liu,et al.  Cyclin E2, a novel human G1 cyclin and activating partner of CDK2 and CDK3, is induced by viral oncoproteins , 1998, Oncogene.

[92]  B. Dynlacht,et al.  Expression of NPAT, a novel substrate of cyclin E-CDK2, promotes S-phase entry. , 1998, Genes & development.

[93]  Michael Ruogu Zhang,et al.  Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. , 1998, Molecular biology of the cell.

[94]  K. Fukasawa,et al.  Human Bub1: a putative spindle checkpoint kinase closely linked to cell proliferation. , 1998, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[95]  Antonio Iavarone,et al.  Regulation of the cdk inhibitor p21 gene during cell cycle progression is under the control of the transcription factor E2F , 1998, Oncogene.

[96]  Brian Schryver,et al.  A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers , 1998, The EMBO journal.

[97]  D. Altieri,et al.  The cancer antiapoptosis mouse survivin gene: characterization of locus and transcriptional requirements of basal and cell cycle-dependent expression. , 1999, Cancer research.

[98]  S. Archer,et al.  Histone acetylation and cancer. , 1999, Current opinion in genetics & development.

[99]  Z. Dominski,et al.  Stem-Loop Binding Protein Facilitates 3′-End Formation by Stabilizing U7 snRNP Binding to Histone Pre-mRNA , 1999, Molecular and Cellular Biology.

[100]  K. Collins,et al.  A telomerase component is defective in the human disease dyskeratosis congenita , 1999, Nature.

[101]  K. Kaibuchi,et al.  Ras-induced transformation and signaling pathway. , 1999, Journal of biochemistry.

[102]  D. Botstein,et al.  The transcriptional program in the response of human fibroblasts to serum. , 1999, Science.

[103]  M. Kirschner,et al.  Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. , 1999, Science.

[104]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[105]  Christian A. Rees,et al.  Distinctive gene expression patterns in human mammary epithelial cells and breast cancers. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[106]  P. Brown,et al.  DNA arrays for analysis of gene expression. , 1999, Methods in enzymology.

[107]  Iain W. Mattaj,et al.  Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation , 1999, Nature.

[108]  R. Goorha,et al.  The mouse mitotic checkpoint gene bub1b, a novel bub1 family member, is expressed in a cell cycle-dependent manner. , 1999, Genomics.

[109]  A. Georgakopoulos,et al.  Presenilin-1 forms complexes with the cadherin/catenin cell-cell adhesion system and is recruited to intercellular and synaptic contacts. , 1999, Molecular cell.

[110]  M. Whitfield,et al.  Stem-Loop Binding Protein, the Protein That Binds the 3′ End of Histone mRNA, Is Cell Cycle Regulated by Both Translational and Posttranslational Mechanisms , 2000, Molecular and Cellular Biology.

[111]  M. Hetzer,et al.  GTP hydrolysis by Ran is required for nuclear envelope assembly. , 2000, Molecular cell.

[112]  K. Vareli,et al.  Nuclear distribution of prothymosin alpha and parathymosin: evidence that prothymosin alpha is associated with RNA synthesis processing and parathymosin with early DNA replication. , 2000, Experimental cell research.

[113]  B. Kennedy,et al.  NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription. , 2000, Genes & development.

[114]  D. Botstein,et al.  Singular value decomposition for genome-wide expression data processing and modeling. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[115]  H. McAdams,et al.  Global analysis of the genetic network controlling a bacterial cell cycle. , 2000, Science.

[116]  H. Gabbert,et al.  Mechanisms of tumor metastasis: cell biological aspects and clinical implications , 2000, Journal of Cancer Research and Clinical Oncology.

[117]  Christian A. Rees,et al.  Molecular portraits of human breast tumours , 2000, Nature.

[118]  F. Marincola,et al.  High-fidelity mRNA amplification for gene profiling , 2000, Nature Biotechnology.

[119]  P. Nurse A Long Twentieth Century of the Cell Cycle and Beyond , 2000, Cell.

[120]  Ash A. Alizadeh,et al.  Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling , 2000, Nature.

[121]  J. Qin,et al.  Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription. , 2000, Genes & development.

[122]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[123]  Christian A. Rees,et al.  Systematic variation in gene expression patterns in human cancer cell lines , 2000, Nature Genetics.

[124]  J. Shah,et al.  Waiting for Anaphase Mad2 and the Spindle Assembly Checkpoint , 2000, Cell.

[125]  K. Wood,et al.  CENP-E as an Essential Component of the Mitotic Checkpoint In Vitro , 2000, Cell.

[126]  K. Vareli,et al.  Nuclear Distribution of Prothymosin α and Parathymosin: Evidence That Prothymosin α Is Associated with RNA Synthesis Processing and Parathymosin with Early DNA Replication , 2000 .

[127]  M. O'Rand,et al.  Characterization of the Histone H1-binding Protein, NASP, as a Cell Cycle-regulated Somatic Protein* , 2000, The Journal of Biological Chemistry.

[128]  J. Labbé,et al.  Mps1 Is a Kinetochore-Associated Kinase Essential for the Vertebrate Mitotic Checkpoint , 2001, Cell.

[129]  E. Hinchcliffe,et al.  "It takes two to tango": understanding how centrosome duplication is regulated throughout the cell cycle. , 2001, Genes & development.

[130]  M. Yaniv,et al.  When the SWI/SNF complex remodels … the cell cycle , 2001, Oncogene.

[131]  Yixian Zheng,et al.  Role of Importin-β in Coupling Ran to Downstream Targets in Microtubule Assembly , 2001, Science.

[132]  Role of Non-histones in Chromosome Structure , 2001 .

[133]  N. Takai,et al.  Expression of polo-like kinase in ovarian cancer is associated with histological grade and clinical stage. , 2001, Cancer letters.

[134]  M. Lei,et al.  Initiating DNA synthesis: from recruiting to activating the MCM complex. , 2001, Journal of cell science.

[135]  H. Piwnica-Worms,et al.  The G2 DNA Damage Checkpoint Delays Expression of Genes Encoding Mitotic Regulators* , 2001, The Journal of Biological Chemistry.

[136]  C. Waterman-Storer,et al.  Importin beta is a mitotic target of the small GTPase Ran in spindle assembly. , 2001, Cell.

[137]  F. Ishikawa,et al.  Human Chromatid Cohesin Component hRad21 Is Phosphorylated in M Phase and Associated with Metaphase Centromeres* , 2001, The Journal of Biological Chemistry.

[138]  T. Kitamura,et al.  MgcRacGAP Is Involved in Cytokinesis through Associating with Mitotic Spindle and Midbody* , 2001, The Journal of Biological Chemistry.

[139]  J. van Marle,et al.  The Human Kinesin-Like Protein RB6K Is under Tight Cell Cycle Control and Is Essential for Cytokinesis , 2001, Molecular and Cellular Biology.

[140]  R. Spang,et al.  Role for E2F in Control of Both DNA Replication and Mitotic Functions as Revealed from DNA Microarray Analysis , 2001, Molecular and Cellular Biology.

[141]  Ronald W. Davis,et al.  Transcriptional regulation and function during the human cell cycle , 2001, Nature Genetics.

[142]  David Botstein,et al.  The Stanford Microarray Database , 2001, Nucleic Acids Res..

[143]  A. Reynolds,et al.  Regulation of Rho GTPases by p120-catenin. , 2001, Current opinion in cell biology.

[144]  A. Bershadsky,et al.  p120 catenin affects cell motility via modulation of activity of Rho-family GTPases: a link between cell-cell contact formation and regulation of cell locomotion. , 2001, Journal of cell science.

[145]  Torsten Wittmann,et al.  The spindle: a dynamic assembly of microtubules and motors , 2001, Nature Cell Biology.

[146]  Karsten Weis,et al.  Importin β Is a Mitotic Target of the Small GTPase Ran in Spindle Assembly , 2001, Cell.

[147]  A. Merdes,et al.  Role of importin-beta in coupling Ran to downstream targets in microtubule assembly. , 2001, Science.

[148]  I. Vernos,et al.  Ran Induces Spindle Assembly by Reversing the Inhibitory Effect of Importin α on TPX2 Activity , 2001, Cell.

[149]  Russ B. Altman,et al.  Missing value estimation methods for DNA microarrays , 2001, Bioinform..

[150]  I. Vernos,et al.  Ran induces spindle assembly by reversing the inhibitory effect of importin alpha on TPX2 activity. , 2001, Cell.

[151]  Donna R. Maglott,et al.  RefSeq and LocusLink: NCBI gene-centered resources , 2001, Nucleic Acids Res..

[152]  It takes two to tango , 2003 .