Identification Of Novel Genes Research Articles

0898 Identification of novel genes and mechanisms involved in bovine myogenic differentiation

0898 Identification of novel genes and mechanisms involved in bovine myogenic differentiation

Identifying N-Glycan Biomarkers in Colorectal Cancer by Mass Spectrometry.

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. Delineating biological markers (biomarkers) for early detection, when treatment is most effective, is key to prevention and long-term survival of patients. Development of reliable biomarkers requires an increased understanding of the CRC biology and the underlying molecular and cellular mechanisms of the disease. With recent advances in new technologies and approaches, tremendous efforts have been put in proteomics and genomics fields to deliver detailed analysis of the two major biomolecules, genes and proteins, to gain a more complete understanding of cellular systems at both genomic and proteomic levels, allowing a mechanistic understanding of the human diseases, including cancer, and opening avenues for identification of novel gene and protein based prognostic and therapeutic markers. Although the importance of glycosylation in modulating protein function has long been appreciated, glycan analysis has been complicated by the diversity of the glycan structures and the large number of potential glycosylation combinations. Driven by recent technological advances, LC-MS/MS based glycomics is gaining momentum in cancer research and holds considerable potential to deliver new glycan-based markers. In our laboratory, we investigated alterations in N-glycosylation associated with CRC malignancy in a panel of CRC cell lines and CRC patient tissues. In an initial study, LC-MS/MS-based N-glycomics were utilized to map the N-glycome landscape associated with a panel of CRC cell lines (LIM1215, LIM1899, and LIM2405). These studies were subsequently extended to paired tumor and nontumorigenic CRC tissues to validate the findings in the cell line. Our studies in both CRC cell lines and tissues identified a strong representation of high mannose and α2,6-linked sialylated complex N-glycans, which corroborate findings from previous studies in CRC and other cancers. In addition, certain unique glycan determinants such as bisecting β1,4-GlcNAcylation and α2,3-sialylation, identified in the metastatic (LIM1215) and aggressive (LIM2405) CRC cell lines, respectively, were shown to be associated with epidermal growth factor receptor (EGFR) expression status. In this Account, we will describe the mass spectrometry based N-glycomics approach utilized in our laboratory to accurately profile the cell- and tissue-specific N-glycomes associated with CRC. We will highlight altered N-glycosylation observed by our studies, consistent with findings from other cancer studies, and discuss how the observed alterations can provide insights into CRC pathogenesis, opening new avenues to identify novel disease-associated glycan markers.

Corrigendum: Identification of novel genes and pathways in carotid atheroma using integrated bioinformatic methods.

Scientific Reports 6: Article number: 18764; published online: 08 January 2016; updated: 19 August 2016. In the original version of this Article, there was an error in Affiliation 1 which was incorrectly given as ‘Department of Health Management, Southern Medical University, Guangzhou 510515, Guangdong, China’.

Detection of Novel QTLs Regulating Grain Size in Extra-Large Grain Rice (Oryza sativa L.) Lines.

BackgroundGrain size is an important trait that affects rice yield. Although many genes that contribute to grain size have been cloned from mutants or by quantitative trait locus (QTL) analysis based on bi-parental mapping, the molecular mechanisms underlying grain-size determination remain poorly understood. In this study, we identified the lines with the largest grain size and detected novel QTLs affecting the grain size.ResultsWe screened the National Institute for Agrobiological Sciences Genebank database and identified two rice lines, BG23 with the widest grain and LG10 with the longest grain. Using these two lines, we performed QTL analysis for grain size. Eight QTLs were detected during the QTL analyses using F2 populations derived from crosses between the large-grain lines BG23 or LG10 and the middle-size grain cultivars Nipponbare and Kasalath. Both BG23 and LG10 possessed large-grain alleles of four major QTLs: GW2, GS3, qSW5/GW5, and GW8. Other three minor QTLs were derived from BG23. However, these QTLs did not explain the differences in grain size between these two lines. Additionally, four QTLs for grain length or width were detected in an F2 population derived from a cross between BG23 and LG10; this population lacked the strong effects of the four major QTLs shared by both parent plants. Of these newly detected QTLs, the effects of two QTLs, GL3b and GL6, were confirmed by progeny testing. Comparison of the length of inner epidermal cells in plants homozygous for BG23 and LG10 alleles indicated that GL3b and GL6 genes regulate cell elongation and cell division, respectively.ConclusionsIn this study, we detected 12 loci including 14 QTLs regulating grain size from two lines with largest grains available in Japanese stock. Of these loci, we confirmed the effect of two gene loci and mapped their candidate region. Identification of novel genes regulating grain size will contribute to our understanding of the molecular mechanisms controlling grain size.Electronic supplementary materialThe online version of this article (doi:10.1186/s12284-016-0109-2) contains supplementary material, which is available to authorized users.

Comparative genomic analysis identified a mutation related to enhanced heterologous protein production in the filamentous fungus Aspergillus oryzae.

Genomic mapping of mutations using next-generation sequencing technologies has facilitated the identification of genes contributing to fundamental biological processes, including human diseases. However, few studies have used this approach to identify mutations contributing to heterologous protein production in industrial strains of filamentous fungi, such as Aspergillus oryzae. In a screening of A. oryzae strains that hyper-produce human lysozyme (HLY), we previously isolated an AUT1 mutant that showed higher production of various heterologous proteins; however, the underlying factors contributing to the increased heterologous protein production remained unclear. Here, using a comparative genomic approach performed with whole-genome sequences, we attempted to identify the genes responsible for the high-level production of heterologous proteins in the AUT1 mutant. The comparative sequence analysis led to the detection of a gene (AO090120000003), designated autA, which was predicted to encode an unknown cytoplasmic protein containing an alpha/beta-hydrolase fold domain. Mutation or deletion of autA was associated with higher production levels of HLY. Specifically, the HLY yields of the autA mutant and deletion strains were twofold higher than that of the control strain during the early stages of cultivation. Taken together, these results indicate that combining classical mutagenesis approaches with comparative genomic analysis facilitates the identification of novel genes involved in heterologous protein production in filamentous fungi.

Mapping transcription factor interactome networks using HaloTag protein arrays

Protein microarrays enable investigation of diverse biochemical properties for thousands of proteins in a single experiment, an unparalleled capacity. Using a high-density system called HaloTag nucleic acid programmable protein array (HaloTag-NAPPA), we created high-density protein arrays comprising 12,000 Arabidopsis ORFs. We used these arrays to query protein-protein interactions for a set of 38 transcription factors and transcriptional regulators (TFs) that function in diverse plant hormone regulatory pathways. The resulting transcription factor interactome network, TF-NAPPA, contains thousands of novel interactions. Validation in a benchmarked in vitro pull-down assay revealed that a random subset of TF-NAPPA validated at the same rate of 64% as a positive reference set of literature-curated interactions. Moreover, using a bimolecular fluorescence complementation (BiFC) assay, we confirmed in planta several interactions of biological interest and determined the interaction localizations for seven pairs. The application of HaloTag-NAPPA technology to plant hormone signaling pathways allowed the identification of many novel transcription factor-protein interactions and led to the development of a proteome-wide plant hormone TF interactome network.

OMICS Technologies and Applications in Sugar Beet.

Sugar beet is a species of the Chenopodiaceae family. It is an important sugar crop that supplies approximately 35% of the sugar in the world. Sugar beet M14 line is a unique germplasm that contains genetic materials from Beta vulgaris L. and Beta corolliflora Zoss. And exhibits tolerance to salt stress. In this review, we have summarized OMICS technologies and applications in sugar beet including M14 for identification of novel genes, proteins related to biotic and abiotic stresses, apomixes and metabolites related to energy and food. An OMICS overview for the discovery of novel genes, proteins and metabolites in sugar beet has helped us understand the complex mechanisms underlying many processes such as apomixes, tolerance to biotic and abiotic stresses. The knowledge gained is valuable for improving the tolerance of sugar beet and other crops to biotic and abiotic stresses as well as for enhancing the yield of sugar beet for energy and food production.

Transcriptome analysis of genes responding to NNV infection in Asian seabass epithelial cells.

Asian seabass is an important food fish in Southeast Asia. Viral nervous necrosis (VNN) disease, triggered by nervous necrosis virus (NNV) infection, has caused mass mortality of Asian seabass larvae, resulting in enormous economic losses in the Asian seabass industry. In order to better understand the complex molecular interaction between Asian seabass and NNV, we investigated the transcriptome profiles of Asian seabass epithelial cells, which play an essential role in immune regulation, after NNV infection. Using the next generation sequencing (NGS) technology, we sequenced mRNA from eight samples (6, 12, 24, 48h post-inoculation) of mock and NNV-infected Asian seabass epithelial cell line, respectively. Clean reads were de novo assembled into a transcriptome consisting of 89026 transcripts with a N50 of 2617bp. Furthermore, 251 differentially expressed genes (DEGs) in response to NNV infection were identified. Top DEGs include protein asteroid homolog 1-like (ASTE1), receptor-transporting protein 3 (RTP3), heat shock proteins 30 (HSP30) and 70 (HSP70), Viperin, interferon regulatory factor 3 (IRF3) and other genes related to innate immunity. Our data suggest that abundant and diverse genes corresponding to NNV infection. The results of this study could also offer vital information not only for identification of novel genes involved in Asian seabass-NNV interaction, but also for our understanding of the molecular mechanism of Asian seabass' response to viral infection. In addition, 24807 simple sequence repeats (SSRs) were detected in the assembled transcriptome, providing valuable resources for studying genetic variations and accelerating quantitative trait loci (QTL) mapping for disease resistance in Asian seabass in the future.

Comparative Proteomic Analysis Reveals Nitrogen Fertilizer Increases Spikelet Number per Panicle in Rice by Repressing Protein Degradation and 14-3-3 Proteins

The spikelet number per panicle is established in the early stages of panicle development. Nitrogen fertilizer application before panicle initiation is known to increase spikelet number, which is one of the most important traits in rice productivity determination. However, the basic proteomic mechanism remains poorly understood. The present study shows that nitrogen fertilizer significantly increased spikelet number and grain yield in rice. Proteomic variations were further analyzed in young panicles at the secondary panicle branch initiation and spikelet meristem initiation under nitrogen fertilizer treatment. Proteomic analysis identified 63 proteins with significant differential accumulation in young panicles under nitrogen fertilizer treatment. Proteolysis represents the largest functional category, which suggests that protein degradation is an important pathway in the response to nitrogen fertilizer. Importantly, nitrogen fertilizer significantly reduced 14-3-3 proteins, which interact with key enzymes associated with carbon and nitrogen metabolism, and the rice FT homologue Hd3a. Real-time PCR revealed that Hd3a signaling is also repressed by nitrogen fertilizer in leaves. This study contributes to a better understanding of the regulation of nitrogen fertilizers in the flowering pathway leading to panicle development. The identification of novel genes provides new insight into the profound impacts of nitrogen fertilizer on panicle development in rice.

Genome Wide Association Study of Seedling and Adult Plant Leaf Rust Resistance in Elite Spring Wheat Breeding Lines.

Leaf rust is an important disease, threatening wheat production annually. Identification of resistance genes or QTLs for effective field resistance could greatly enhance our ability to breed durably resistant varieties. We applied a genome wide association study (GWAS) approach to identify resistance genes or QTLs in 338 spring wheat breeding lines from public and private sectors that were predominately developed in the Americas. A total of 46 QTLs were identified for field and seedling traits and approximately 20–30 confer field resistance in varying degrees. The 10 QTLs accounting for the most variation in field resistance explained 26–30% of the total variation (depending on traits: percent severity, coefficient of infection or response type). Similarly, the 10 QTLs accounting for most of the variation in seedling resistance to different races explained 24–34% of the variation, after correcting for population structure. Two potentially novel QTLs (QLr.umn-1AL, QLr.umn-4AS) were identified. Identification of novel genes or QTLs and validation of previously identified genes or QTLs for seedling and especially adult plant resistance will enhance understanding of leaf rust resistance and assist breeding for resistant wheat varieties. We also developed computer programs to automate field and seedling rust phenotype data conversions. This is the first GWAS study of leaf rust resistance in elite wheat breeding lines genotyped with high density 90K SNP arrays.

Acute blockade of the Caenorhabditis elegans dopamine transporter DAT-1 by the mammalian norepinephrine transporter inhibitor nisoxetine reveals the influence of genetic modifications of dopamine signaling in vivo

Modulation of neurotransmission by the catecholamine dopamine (DA) is conserved across phylogeny. In the nematode Caenorhabditis elegans, excess DA signaling triggers Swimming-Induced Paralysis (Swip), a phenotype first described in animals with loss of function mutations in the presynaptic DA transporter (dat-1). Swip has proven to be a phenotype suitable for the identification of novel dat-1 mutations as well as the identification of novel genes that impact DA signaling. Pharmacological manipulations can also induce Swip, though the reagents employed to date lack specificity and potency, limiting their use in evaluation of dat-1 expression and function. Our lab previously established the mammalian norepinephrine transporter (NET) inhibitor nisoxetine to be a potent antagonist of DA uptake conferred by DAT-1 following heterologous expression. Here we demonstrate the ability of low (μM) concentrations of nisoxetine to trigger Swip within minutes of incubation, with paralysis dependent on DA release and signaling, and non-additive with Swip triggered by dat-1 deletion. Using nisoxetine in combination with genetic mutations that impact DA release, we further demonstrate the utility of the drug for demonstrating contributions of presynaptic DA receptors and ion channels to Swip. Together, these findings reveal nisoxetine as a powerful reagent for monitoring multiple dimensions of DA signaling in vivo, thus providing a new resource that can be used to evaluate contributions of dat-1 and other genes linked to DA signaling without the potential for compensations that attend constitutive genetic mutations.

Identification of novel genes and pathways in carotid atheroma using integrated bioinformatic methods.

Atherosclerosis is the primary cause of cardiovascular events and its molecular mechanism urgently needs to be clarified. In our study, atheromatous plaques (ATH) and macroscopically intact tissue (MIT) sampled from 32 patients were compared and an integrated series of bioinformatic microarray analyses were used to identify altered genes and pathways. Our work showed 816 genes were differentially expressed between ATH and MIT, including 443 that were up-regulated and 373 that were down-regulated in ATH tissues. GO functional-enrichment analysis for differentially expressed genes (DEGs) indicated that genes related to the “immune response” and “muscle contraction” were altered in ATHs. KEGG pathway-enrichment analysis showed that up-regulated DEGs were significantly enriched in the “FcεRI-mediated signaling pathway”, while down-regulated genes were significantly enriched in the “transforming growth factor-β signaling pathway”. Protein-protein interaction network and module analysis demonstrated that VAV1, SYK, LYN and PTPN6 may play critical roles in the network. Additionally, similar observations were seen in a validation study where SYK, LYN and PTPN6 were markedly elevated in ATH. All in all, identification of these genes and pathways not only provides new insights into the pathogenesis of atherosclerosis, but may also aid in the development of prognostic and therapeutic biomarkers for advanced atheroma.

Identification of novel gene and pathway targets for human epilepsy treatment.

BackgroundThe aim of this study was to explore epilepsy-related mechanism so as to figure out the possible targets for epilepsy treatment.MethodsThe gene expression profile dataset GES32534 was downloaded from Gene Expression Omnibus database. We identified the differentially expressed genes (DEGs) by Affy package. Then the DEGs were used to perform gene ontology (GO) and pathway enrichment analyses. Furthermore, a protein–protein interaction (PPI) network was constructed with the DEGs followed by co-expression modules construction and analysis.ResultsTotal 420 DEGs were screened out, including 214 up-regulated and 206 down-regulated genes. Functional enrichment analysis revealed that down-regulated genes were mainly involved in the process of immunity regulation and biological repairing process while up-regulated genes were closely related to transporter activity. PPI network analysis showed the top ten genes with high degrees were all down-regulated, among which FN1 had the highest degree. The up-regulated and down-regulated DEGs in the PPI network generated two obvious sub-co-expression modules, respectively. In up-co-expression module, SCN3B (sodium channel, voltage gated, type III beta subunit) was enriched in GO:0006814 ~ sodium ion transport. In down-co-expression module, C1QB (complement C1s), C1S (complement component 1, S subcomponent) and CFI (complement factor I) were enriched in GO:0006955 ~ immune response.ConclusionThe immune response and complement system play a major role in the pathogenesis of epilepsy. Additionally, C1QB, C1S, CFI, SCN3B and FN1 may be potential therapeutic targets for epilepsy.

Computational Identification of Novel Genes: Current and Future Perspectives.

While it has long been thought that all genomic novelties are derived from the existing material, many genes lacking homology to known genes were found in recent genome projects. Some of these novel genes were proposed to have evolved de novo, ie, out of noncoding sequences, whereas some have been shown to follow a duplication and divergence process. Their discovery called for an extension of the historical hypotheses about gene origination. Besides the theoretical breakthrough, increasing evidence accumulated that novel genes play important roles in evolutionary processes, including adaptation and speciation events. Different techniques are available to identify genes and classify them as novel. Their classification as novel is usually based on their similarity to known genes, or lack thereof, detected by comparative genomics or against databases. Computational approaches are further prime methods that can be based on existing models or leveraging biological evidences from experiments. Identification of novel genes remains however a challenging task. With the constant software and technologies updates, no gold standard, and no available benchmark, evaluation and characterization of genomic novelty is a vibrant field. In this review, the classical and state-of-the-art tools for gene prediction are introduced. The current methods for novel gene detection are presented; the methodological strategies and their limits are discussed along with perspective approaches for further studies.

Genome Analysis of Rice Genetic Resources for the Identification of Novel Genes and Alleles for Biotic Stress Resistance

Genome Analysis of Rice Genetic Resources for the Identification of Novel Genes and Alleles for Biotic Stress Resistance

Schistosoma mansoni Egg, Adult Male and Female Comparative Gene Expression Analysis and Identification of Novel Genes by RNA-Seq

BackgroundSchistosomiasis is one of the most prevalent parasitic diseases worldwide and is a public health problem. Schistosoma mansoni is the most widespread species responsible for schistosomiasis in the Americas, Middle East and Africa. Adult female worms (mated to males) release eggs in the hepatic portal vasculature and are the principal cause of morbidity. Comparative separate transcriptomes of female and male adult worms were previously assessed with using microarrays and Serial Analysis of Gene Expression (SAGE), thus limiting the possibility of finding novel genes. Moreover, the egg transcriptome was analyzed only once with limited bacterially cloned cDNA libraries.Methodology/Principal findingsTo compare the gene expression of S. mansoni eggs, females, and males, we performed RNA-Seq on these three parasite forms using 454/Roche technology and reconstructed the transcriptome using Trinity de novo assembly. The resulting contigs were mapped to the genome and were cross-referenced with predicted Smp genes and H3K4me3 ChIP-Seq public data. For the first time, we obtained separate, unbiased gene expression profiles for S. mansoni eggs and female and male adult worms, identifying enriched biological processes and specific enriched functions for each of the three parasite forms. Transcripts with no match to predicted genes were analyzed for their protein-coding potential and the presence of an encoded conserved protein domain. A set of 232 novel protein-coding genes with putative functions related to reproduction, metabolism, and cell biogenesis was detected, which contributes to the understanding of parasite biology.Conclusions/SignificanceLarge-scale RNA-Seq analysis using de novo assembly associated with genome-wide information for histone marks in the vicinity of gene models constitutes a new approach to transcriptome analysis that has not yet been explored in schistosomes. Importantly, all data have been consolidated into a UCSC Genome Browser search- and download-tool (http://schistosoma.usp.br/). This database provides new ways to explore the schistosome genome and transcriptome and will facilitate molecular research on this important parasite.

THE SPECTRUM OF CONGENITAL MYOPATHIES IN ROMANIA – A PATHOLOGICAL RETROSPECTIVE STUDY

Objectives. Congenital myopathies (CM) are a highly heterogeneous group of disorders with genetic cause, characterized by motor deficit and weakness usually manifesting in the neonatal period, with slowly progressive or non-progressive course and affecting both sexes. MC classification has undergone many changes over time, and in recent years molecular genetic studies have enabled identification of novel genes and mutations, thus increasing the diagnostic complexity. We wanted to study the incidence and morphological features of the CM cases diagnosed by muscle biopsy in the Pathology Department of Colentina University Hospital over a period of 10 years (09.2005- 09.2015). Materials and methods. We retrospectively reviewed all the muscle biopsies diagnosed with different types of CM. Muscle biopsies were performed and specifically processed using routine and special stains on cryosections, semithin and ultrathin sections for ultrastructural examination. In all the cases we reassessed the clinical and laboratory data. Results. From a number of 1,530 peripheral nerve and muscle biopsies performed and analyzed in the 10 years period we diagnosed CM in 15 cases, representing 1.03% of the total. Of these, five were “central core myopathies”, five centronuclear/myotubular myopathies, one case of nemaline myopathy, one case of “reducing body myopathy” and three cases with congenital fiber type disproportion. Reassessment of morphological data in the clinical context allowed us to identify numerous overlaps between subtypes both in the clinical and pathological picture. Conclusions. The reduced number of MC identified in our country suggests that these diseases are probably underdiagnosed or diagnosed late, requiring a better understanding of the various clinical and pathological particularities. In the accurate diagnostic algorithm, muscle biopsy remains essential to establish the type of CM and thus to direct genetic tests.

Analysis of nucleosome positioning landscapes enables gene discovery in the human malaria parasite Plasmodium falciparum.

BackgroundPlasmodium falciparum, the deadliest malaria-causing parasite, has an extremely AT-rich (80.7 %) genome. Because of high AT-content, sequence-based annotation of genes and functional elements remains challenging. In order to better understand the regulatory network controlling gene expression in the parasite, a more complete genome annotation as well as analysis tools adapted for AT-rich genomes are needed. Recent studies on genome-wide nucleosome positioning in eukaryotes have shown that nucleosome landscapes exhibit regular characteristic patterns at the 5’- and 3’-end of protein and non-protein coding genes. In addition, nucleosome depleted regions can be found near transcription start sites. These unique nucleosome landscape patterns may be exploited for the identification of novel genes. In this paper, we propose a computational approach to discover novel putative genes based exclusively on nucleosome positioning data in the AT-rich genome of P. falciparum.ResultsUsing binary classifiers trained on nucleosome landscapes at the gene boundaries from two independent nucleosome positioning data sets, we were able to detect a total of 231 regions containing putative genes in the genome of Plasmodium falciparum, of which 67 highly confident genes were found in both data sets. Eighty-eight of these 231 newly predicted genes exhibited transcription signal in RNA-Seq data, indicative of active transcription. In addition, 20 out of 21 selected gene candidates were further validated by RT-PCR, and 28 out of the 231 genes showed significant matches using BLASTN against an expressed sequence tag (EST) database. Furthermore, 108 (47 %) out of the 231 putative novel genes overlapped with previously identified but unannotated long non-coding RNAs. Collectively, these results provide experimental validation for 163 predicted genes (70.6 %). Finally, 73 out of 231 genes were found to be potentially translated based on their signal in polysome-associated RNA-Seq representing transcripts that are actively being translated.ConclusionOur results clearly indicate that nucleosome positioning data contains sufficient information for novel gene discovery. As distinct nucleosome landscapes around genes are found in many other eukaryotic organisms, this methodology could be used to characterize the transcriptome of any organism, especially when coupled with other DNA-based gene finding and experimental methods (e.g., RNA-Seq).Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2214-9) contains supplementary material, which is available to authorized users.

Sleep as a biological problem: an overview of frontiers in sleep research.

Sleep is a physiological process not only for the rest of the body but also for several brain functions such as mood, memory, and consciousness. Nevertheless, the nature and functions of sleep remain largely unknown due to its extremely complicated nature and lack of optimized technology for the experiments. Here we review the recent progress in the biology of the mammalian sleep, which covers a wide range of research areas: the basic knowledge about sleep, the physiology of cerebral cortex in sleeping animals, the detailed morphological features of thalamocortical networks, the mechanisms underlying fluctuating activity of autonomic nervous systems during rapid eye movement sleep, the cutting-edge technology of tissue clearing for visualization of the whole brain, the ketogenesis-mediated homeostatic regulation of sleep, and the forward genetic approach for identification of novel genes involved in sleep. We hope this multifaceted review will be helpful for researchers who are interested in the biology of sleep.

Aurora Kinase A Is Upregulated in Cutaneous T-Cell Lymphoma and Represents a Potential Therapeutic Target

Cutaneous T-cell lymphomas (CTCLs) form a heterogeneous group of non-Hodgkin's lymphomas characterized by only poor prognosis in advanced stage. Despite significant progress made in the identification of novel genes and pathways involved in the pathogenesis of cutaneous lymphoma, the therapeutic value of these findings has still to be proven. Here, we demonstrate by gene expression arrays that Aurora kinase A is one of the highly overexpressed genes of the serine/threonine kinase in CTCL. The finding was confirmed by quantitative reverse transcriptase-PCR, western blotting, and immunohistochemistry in CTCL cell lines and primary patient samples. Moreover, treatment with a specific Aurora kinase A inhibitor blocks cell proliferation by inducing cell cycle arrest in G2 phase, as well as apoptosis in CTCL cell lines. These data provide a promising rationale for using Aurora kinase A inhibition as a therapeutic modality of CTCL.