Function Of Translationally Controlled Tumor Protein Research Articles

TCTP regulates genotoxic stress and tumorigenicity via intercellular vesicular signaling

Oncogenic intercellular signaling is regulated by extracellular vesicles (EVs), but the underlying mechanisms remain mostly unclear. Since TCTP (translationally controlled tumor protein) is an EV component, we investigated whether it has a role in genotoxic stress signaling and malignant transformation. By generating a Tctp-inducible knockout mouse model (Tctp–/f–), we report that Tctp is required for genotoxic stress-induced apoptosis signaling via small EVs (sEVs). Human breast cancer cells knocked-down for TCTP show impaired spontaneous EV secretion, thereby reducing sEV-dependent malignant growth. Since Trp53–/– mice are prone to tumor formation, we derived tumor cells from Trp53–/–;Tctp–/f– double mutant mice and describe a drastic decrease in tumori-genicity with concomitant decrease in sEV secretion and content. Remarkably, Trp53–/–;Tctp–/f– mice show highly prolonged survival. Treatment of Trp53–/– mice with sertraline, which inhibits TCTP function, increases their survival. Mechanistically, TCTP binds DDX3, recruiting RNAs, including miRNAs, to sEVs. Our findings establish TCTP as an essential protagonist in the regulation of sEV-signaling in the context of apoptosis and tumorigenicity.

Targeting inhibition of TCTP could inhibit proliferation and induce apoptosis in AML cells

Translationally controlled tumor protein (TCTP) is a highly conserved multifunctional protein, which participates in many important physiological processes. Recently, the roles of TCTP in cell proliferation and apoptosis, especially its close relationship with various tumors, have attracted widespread attention. In this study, we found that the protein level of TCTP was significantly reduced in acute promyelocytic leukemia cell line NB4 transfected with retinoic acid-induced gene G (RIG-G). The RIG-G was found in our previous work as a key mediator of anti-proliferative activity in retinoid/interferon-related pathways. Here, we tried to further explore the function of TCTP in the development of acute myeloid leukemia (AML) from different levels. Our results showed that inhibiting TCTP expression could attenuate AML cells proliferation and induce apoptosis both in AML cell lines and in xenograft of NOD-SCID mice. In addition, either compared with patients in complete remission or non-leukemia patients, we detected that the expression of TCTP was generally high in the fresh bone marrow of AML patients, suggesting that there was a certain correlation between TCTP and AML disease progression. Taken together, our study revealed the role of TCTP in AML development, and provided a potential target for AML treatment.

The functional link between TCTP and Drsl1 in deltamethrin-stressed Drosophila Kc cells

Translationally controlled tumor protein (TCTP) is a growth and development related protein found in almost all eukaryotes and can be involved in a variety of cellular life activities. Our previous studies found that TCTP is involved in the response of Drosophila Kc cells to deltamethrin (DM) stimulation, and it may be a candidate gene related to DM stress. Therefore, we would further investigate the functions of TCTP and its mechanism under DM stress. The qPCR results showed that the expression level of Drsl1 increasing first and then decreasing with the change of DM concentration and treatment duration. The optimal concentration was 20 ppm and the optimal time was 24 h. qPCR and WB results together showed that the expression levels of TCTP and Drsl1 were positively correlated. The flow cytometry showed the expression levels of TCTP and Drsl1 in deltamethrin-stressed cells are related to apoptosis. The apoptosis rate reached the highest level in the cells with simultaneous interference of both genes. Taken together, our data mainly suggest that TCTP interacts with Drsl1 in response to DM stress in Drosophila Kc cells, which helps to investigate the mechanisms of DM toxicity and the mechanisms by which insects develop resistance to it.

Translationally controlled tumor protein: the mediator promoting cancer invasion and migration and its potential clinical prospects.

Translationally controlled tumor protein (TCTP) is a highly conserved multifunctional protein localized in the cytoplasm and nucleus of eukaryotic cells. It is secreted through exosomes and its degradation is associated with the ubiquitin-proteasome system (UPS), heat shock protein 27 (Hsp27), and chaperone-mediated autophagy (CMA). Its structure contains three α‍-helices and eleven β‍-strands, and features a helical hairpin as its hallmark. TCTP shows a remarkable similarity to the methionine-R-sulfoxide reductase B (MsrB) and mammalian suppressor of Sec4 (Mss4/Dss4) protein families, which exerts guanine nucleotide exchange factor (GEF) activity on small guanosine triphosphatase (GTPase) proteins, suggesting that some functions of TCTP may at least depend on its GEF action. Indeed, TCTP exerts GEF activity on Ras homolog enriched in brain (Rheb) to boost the growth and proliferation of Drosophila cells. TCTP also enhances the expression of cell division control protein 42 homolog (Cdc42) to promote cancer cell invasion and migration. Moreover, TCTP regulates cytoskeleton organization by interacting with actin microfilament (MF) and microtubule (MT) proteins and inducing the epithelial-mesenchymal transition (EMT) process. In essence, TCTP promotes cancer cell movement. It is usually highly expressed in cancerous tissues and thus reduces patient survival; meanwhile, drugs can target TCTP to reduce this effect. In this review, we summarize the mechanisms of TCTP in promoting cancer invasion and migration, and describe the current inhibitory strategy to target TCTP in cancerous diseases.

TCTP participates in hepatic metabolism by regulating gene expression involved in insulin resistance.

Translationally controlled tumor protein (TCTP) has various cellular functions and molecular interactions, many related to its growth-promoting and antiapoptotic properties. Recently, TCTP expression was reported to increases in insulin-resistant mice fed with high-fat diet. TCTP is a multifunctional protein, but its role in liver metabolism is unclear. Here, we investigated the function and mechanism of TCTP in HepG2 cells. Knock-down of TCTP led to 287 differentially expressed genes (DEGs) that were highly associated with cellular apoptosis and signal response, TNF and NF-κB signaling pathways, glycolysis/gluconeogenesis, insulin resistance, FoxO and insulin signaling pathways, adipocytokine and AMPK signaling pathways. shTCTP downregulated the expression of the key gluconeogenesis enzyme phosphoenolpyruvate carboxykinase (PCK1). Furthermore, TCTP regulated the alternative splicing of genes enriched in the phospholipid biosynthetic process and glycerophospholipid metabolism. We further showed that shTCTP down-regulated the intracellular levels of triglyceride and total cholesterol. Our results showed that TCTP regulates the liver cell transcriptome at both the transcriptional and alternative splicing levels. The TCTP regulatory network predicts the biological functions of TCTP in glucose and lipid metabolism, and also insulin resistance, which may be associated with liver metabolism and diseases such as nonalcoholic fatty liver disease.

Dysregulation of TCTP in Biological Processes and Diseases.

Translationally controlled tumor protein (TCTP), also called histamine releasing factor (HRF) or fortilin, is a multifunctional protein present in almost all eukaryotic organisms. TCTP is involved in a range of basic cell biological processes, such as promotion of growth and development, or cellular defense in response to biological stresses. Cellular TCTP levels are highly regulated in response to a variety of physiological signals, and regulatory mechanism at various levels have been elucidated. Given the importance of TCTP in maintaining cellular homeostasis, it is not surprising that dysregulation of this protein is associated with a range of disease processes. Here, we review recent progress that has been made in the characterisation of the basic biological functions of TCTP, in the description of mechanisms involved in regulating its cellular levels and in the understanding of dysregulation of TCTP, as it occurs in disease processes such as cancer.

Comprehensive analysis of Translationally Controlled Tumor Protein (TCTP) provides insights for lineage-specific evolution and functional divergence.

BackgroundTranslationally controlled tumor protein (TCTP) is a conserved, multifunctional protein involved in numerous cellular processes in eukaryotes. Although the functions of TCTP have been investigated sporadically in animals, invertebrates, and plants, few lineage-specific activities of this molecule, have been reported. An exception is in Arabidopsis thaliana, in which TCTP (AtTCTP1) functions in stomatal closuer by regulating microtubule stability. Further, although the development of next-generation sequencing technologies has facilitated the analysis of many eukaryotic genomes in public databases, inter-kingdom comparative analyses using available genome information are comparatively scarce.MethodologyTo carry out inter-kingdom comparative analysis of TCTP, TCTP genes were identified from 377 species. Then phylogenetic analysis, prediction of protein structure, molecular docking simulation and molecular dynamics analysis were performed to investigate the evolution of TCTP genes and their binding proteins.ResultsA total of 533 TCTP genes were identified from 377 eukaryotic species, including protozoa, fungi, invertebrates, vertebrates, and plants. Phylogenetic and secondary structure analyses reveal lineage-specific evolution of TCTP, and inter-kingdom comparisons highlight the lineage-specific emergence of, or changes in, secondary structure elements in TCTP proteins from different kingdoms. Furthermore, secondary structure comparisons between TCTP proteins within each kingdom, combined with measurements of the degree of sequence conservation, suggest that TCTP genes have evolved to conserve protein secondary structures in a lineage-specific manner. Additional tertiary structure analysis of TCTP-binding proteins and their interacting partners and docking simulations between these proteins further imply that TCTP gene variation may influence the tertiary structures of TCTP-binding proteins in a lineage-specific manner.ConclusionsOur analysis suggests that TCTP has undergone lineage-specific evolution and that structural changes in TCTP proteins may correlate with the tertiary structure of TCTP-binding proteins and their binding partners in a lineage-specific manner.

Homology modeling and molecular dynamics simulations of a cassava translationally controlled tumor protein (MeTCTP)

Abiotic stresses are responsible for serious productivity and yield losses in many crops worldwide. Thus, there is great relevance in the prospection of plant molecular components, including gene products related to endogenous defense mechanisms, providing insights into plant tolerance. The TCTP (translationally controlled tumor protein) is a protein family highly conserved in eukaryotic organisms and related to abiotic stress responses. Recently, we have verified the thermotolerance in Escherichia coli and in vitro chaperone-like activity of TCTP from cassava (MeTCTP). To increase the understanding about the roles of MeTCTP in response to abiotic stresses, here we performed structural analysis of MeTCTP through homology modeling and molecular dynamics simulations, generating a three-dimensional model for calcium-binding to MeTCTP, since the calcium binding property is critical for the role of many proteins that are regulated in response to abiotic stress. Results presented here provided the first prediction for calcium-binding to MeTCTP by molecular dynamics simulations and the main residues related to this interaction. In addition, such results can contribute for the understanding of TCTP function against abiotic stress under in vivo conditions in cassava, as well as in other plants, such as Arabidopsis thaliana.

Radiosensitivity of Cancer Cells Is Regulated by Translationally Controlled Tumor Protein.

Translationally controlled tumor protein (TCTP) is a ubiquitous multifunctional protein that is essential for cell survival. This study reveals that the regulation of radiosensitivity of cancer cells is yet another function of TCTP. The relationship between endogenous TCTP levels and sensitivity to radiation was examined in breast cancer cell lines (T47D, MDA-MB-231, and MCF7) and lung cancer cells lines (A549, H1299, and H460). Cancer cells with high expression levels of TCTP were more resistant to radiation. TCTP overexpression inhibited radiation-induced cell death, while silencing TCTP led to an increase in radiosensitivity. DNA damage in the irradiated TCTP-silenced A549 cells was greater than in irradiated control shRNA-transfected A549 cells. p53, a well-known reciprocal regulator of TCTP, was increased in irradiated TCTP down-regulated A549 cells. Moreover, introduction of p53 siRNA in TCTP knocked-down A549 cells abrogated the increased radiosensitivity induced by TCTP knockdown. An in vivo xenograft study also confirmed enhanced radiosensitivity in TCTP down-regulated A549 cells. These findings suggest that TCTP has the potential to serve as a therapeutic target to overcome radiation resistance in cancer, a major problem for the effective treatment of cancers.

Distinct 3' UTRs regulate the life-cycle-specific expression of two TCTP paralogs in Trypanosoma brucei.

ABSTRACTThe translationally controlled tumor protein (TCTP; also known as TPT1 in mammals) is highly conserved and ubiquitously expressed in eukaryotes. It is involved in growth and development, cell cycle progression, protection against cellular stresses and apoptosis, indicating the multifunctional role of the protein. Here, for the first time, we characterize the expression and function of TCTP in the human and animal pathogen, Trypanosoma brucei. We identified two paralogs (TCTP1 and TCTP2) that are differentially expressed in the life cycle of the parasite. The genes have identical 5′ untranslated regions (UTRs) and almost identical open-reading frames. The 3′UTRs differ substantially in sequence and length, and are sufficient for the exclusive expression of TCTP1 in procyclic- and TCTP2 in bloodstream-form parasites. Furthermore, we characterize which parts of the 3′UTR are needed for TCTP2 mRNA stability. RNAi experiments demonstrate that TCTP1 and TCTP2 expression is essential for normal cell growth in procyclic- and bloodstream-form parasites, respectively. Depletion of TCTP1 in the procyclic form cells leads to aberrant cell and mitochondrial organelle morphology, as well as enlarged, and a reduced number of, acidocalcisomes.

Structure-Function Relationship of TCTP.

The translationally controlled tumor protein (TCTP) is a small, multifunctional protein found in most, if not all, eukaryotic lineages, involved in a myriad of key regulatory processes. Among these, the control of proliferation and inhibition of cell death, as well as differentiation, are the most important, and it is probable that other responses are derived from the ability of TCTP to influence them in both unicellular and multicellular organisms. In the latter, an additional function for TCTP stems from its capacity to be secreted via a nonclassical pathway and function in a non-cell autonomous (paracrine) manner, thus affecting the responses of neighboring or distant cells to developmental or environmental stimuli (as in the case of serum TCTP/histamine-releasing factor in mammals and phloem TCTP in Arabidopsis). The additional ability to traverse membranes without a requirement for transmembrane receptors adds to its functional flexibility. The long-distance transport of TCTP mRNA and protein in plants via the vascular system supports the notion that an important aspect of TCTP function is its ability to influence the response of neighboring and distant cells to endogenous and exogenous signals in a supracellular manner. The predicted tridimensional structure of TCTPs indicates a high degree of conservation, more than its amino acid sequence similarity could suggest. However, subtle differences in structure could lead to different activities, as evidenced by TCTPs secreted by Plasmodium spp. Similar structural variations in animal and plant TCTPs, likely the result of convergent evolution, could lead to deviations from the canonical function of this group of proteins, which could have an impact from a biomedical and agricultural perspectives.

Translationally Controlled Tumor Protein Stimulates Dopamine Release from PC12 Cells via Ca2+-Independent Phospholipase A₂ Pathways.

The translationally controlled tumor protein (TCTP), initially identified as a tumor- and growth-related protein, is also known as a histamine-releasing factor (HRF). TCTP is widely distributed in the neuronal systems, but its function is largely uncharacterized. Here, we report a novel function of TCTP in the neurotransmitter release from a neurosecretory, pheochromocytoma (PC12) cells. Treatment with recombinant TCTP (rTCTP) enhanced both basal and depolarization (50 mM KCl)-evoked [3H]dopamine release in concentration- and time-dependent manners. Interestingly, even though rTCTP induced the increase in intracellular calcium levels ([Ca2+]i), the rTCTP-driven effect on dopamine release was mediated by a Ca2+-independent pathway, as evidenced by the fact that Ca2+-modulating agents such as Ca2+ chelators and a voltage-gated L-type Ca2+-channel blocker did not produce any changes in rTCTP-evoked dopamine release. In a study to investigate the involvement of phospholipase A2 (PLA2) in rTCTP-induced dopamine release, the inhibitor for Ca2+-independent PLA2 (iPLA2) produced a significant inhibitory effect on rTCTP-induced dopamine release, whereas this release was not significantly inhibited by Ca2+-dependent cytosolic PLA2 (cPLA2) and secretory PLA2 (sPLA2) inhibitors. We found that rTCTP-induced dopamine release from neuronal PC12 cells was modulated by a Ca2+-independent mechanism that involved PLA2 in the process, suggesting the regulatory role of TCTP in the neuronal functions.

SiRNA targeting TCTP suppresses osteosarcoma cell growth and induces apoptosis in vitro and in vivo.

Osteosarcoma (OS) remains the most frequent primary malignant bone tumor in adolescents. However, the molecular cause of the disease is poorly elucidated. In the present study, we primarily found that translationally controlled tumor protein (TCTP) was overexpressed in human OS tissues and cell lines. To investigate the function of TCTP in OS cell growth, an RNA interference lentivirus system was employed to deplete TCTP expression in Saos-2 and U2OS cell lines. Specific knockdown of TCTP significantly impaired cell proliferation and colony-formation capacity in both OS cell lines. Moreover, depletion of TCTP caused a significant accumulation of OS cells in the S phase and eventually induced cell apoptosis. Expression levels of the G2/M phase regulators cyclin B1 and Cdc25A were decreased, and apoptotic markers Bad and caspase-3 were increased in both OS cell lines after depletion of TCTP. Furthermore, depletion of TCTP potently inhibited the growth of xenografts in nude mice. Our results indicate that inhibition of TCTP expression exerts potential antitumor activity and may be a novel therapeutic approach in human OS.

Evolutionarily Conserved Binding of Translationally Controlled Tumor Protein to Eukaryotic Elongation Factor 1B

Translationally controlled tumor protein (TCTP) is an abundant protein that is highly conserved in eukaryotes. However, its primary function is still not clear. Human TCTP interacts with the metazoan-specific eukaryotic elongation factor 1Bδ (eEF1Bδ) and inhibits its guanine nucleotide exchange factor (GEF) activity, but the structural mechanism remains unknown. The interaction between TCTP and eEF1Bδ was investigated by NMR titration, structure determination, paramagnetic relaxation enhancement, site-directed mutagenesis, isothermal titration calorimetry, and HADDOCK docking. We first demonstrated that the catalytic GEF domain of eEF1Bδ is not responsible for binding to TCTP but rather a previously unnoticed central acidic region (CAR) domain in eEF1Bδ. The mutagenesis data and the structural model of the TCTP-eEF1Bδ CAR domain complex revealed the key binding residues. These residues are highly conserved in eukaryotic TCTPs and in eEF1B GEFs, including the eukaryotically conserved eEF1Bα, implying the interaction may be conserved in all eukaryotes. Interactions were confirmed between TCTP and the eEF1Bα CAR domain for human, fission yeast, and unicellular photosynthetic microalgal proteins, suggesting that involvement in protein translation through the conserved interaction with eEF1B represents a primary function of TCTP.

Long distance movement of an Arabidopsis Translationally Controlled Tumor Protein (AtTCTP2) mRNA and protein in tobacco.

Translationally Controlled Tumor Protein (TCTP) is an almost ubiquitous protein found in eukaryotes, fundamental for the regulation of development and general growth. The multiple functions of TCTP have been inferred from its involvement in several cell pathways, but the specific function of TCTP is still not known in detail. On the other hand, TCTP seems to respond to a plethora of external signals, and appears to be regulated at the transcriptional and/or translational levels by mechanisms yet to be determined. In the present work, we analyzed the capacity of AtTCTP2 gene products (mRNA and protein) to translocate long distance through tobacco heterografts (transgenic/WT and WT/transgenic). The results indicate that both AtTCTP2 mRNA and protein are capable of moving long distance in both directions (stock-scion and scion-stock) with a tendency for movement from source to sink tissue (stock to scion). Interestingly, aerial roots emerged only in heterografts where the protein was detected in both stock and scion, suggesting a correlation between the presence of AtTCTP2 and aerial root appearance. More detailed analysis showed that these aerial roots harbored the transgene and expressed both transcript and protein. In addition, the protein localization pattern in transgenic aerial and primary roots was basically the same, indicating specific nuclear destination in roots, but also in leaves. These findings provide an approach to understand the role of long-distance movement in the function of plant TCTPs, supporting the notion that some of these act in a non-cell autonomous manner, as the human counterpart, the Histamine Releasing Factor (HRF).

The first characterization of gene structure and biological function for echinoderm translationally controlled tumor protein (TCTP)

Translationally controlled tumor protein (TCTP) is a multifunctional protein that existed ubiquitously in different eukaryote species and distributed widely in various tissues and cell types. In this study, the gene structure and biological function of TCTP were first characterized in echinoderm. An echinoderm TCTP named StmTCTP was identified from sea cucumber (Stichopus monotuberculatus) by expression sequence tag (EST) analysis and rapid amplification of cDNA ends (RACE) approach. The StmTCTP cDNA is 1219 bp in length, containing a 5′-untranslated region (UTR) of 77 bp, a 3′-UTR of 623 bp and an open reading frame (ORF) of 519 bp that encoding a protein of 172 amino acids with a deduced molecular weight of 19.80 kDa and a predicted isolectric point of 4.66. Two deduced signal signatures termed TCTP1 and TCTP2, a microtubule binding domain, a Ca2+ binding domain and the conserved residues forming Rab GTPase binding surface were found in the StmTCTP amino acid sequence. For the gene structure, StmTCTP contains four exons separated by three introns. The anti-oxidation and heat shock protein activities of recombinant TCTP protein were also demonstrated in this study. In addition, the expression of StmTCTP was found to be significantly upregulated by polyriboinosinic polyribocytidylic acid [poly (I:C)], lipopolysaccharides (LPS) or inactivated bacteria challenge in in vitro primary culture experiments of coelomocytes, suggested that the sea cucumber TCTP might play critical roles not only in the defense against oxidative and thermal stresses, but also in the innate immune defense against bacterial and viral infections.

Bioinformatic analysis for structure and function of TCTP from Spirometra mansoni

ObjectiveTo predict structure and function of translationally controlled tumor protein (TCTP) from Spirometra mansoni by bioinformatics technology, and to provide a theoretical basis for further study. MethodsOpen reading frame (ORF) of EST sequence from Spirometra mansoni was obtained by ORF finder and was translated into amino acid residue by DNAclub. The structure domain was analyzed by Blast. By the method of online analysis tools: Protparam, InterProScan, protscale, SignalP-3.0, PSORT II, BepiPred, TMHMM, VectorNTI Suite 9 packages and Phyre2, the structure and function of the protein were predicted and analyzed. ResultsThe results showed that the EST sequence was Sm TCTP with 173 amino acid residues, theoretical molecular weight was 19 872.0 Da. The protein has the closest evolutionary status with Clonorchis sinensis, Schistosoma mansoni, and Schistosoma japonicum. Then it had no signal peptide site and transmembrane domain. Secondary structure of TCTP contained two α -helices and eight β -strands. ConclusionsSm TCTP was a variety of biological functions of protein that may be used as a vaccine candidate molecule and drug target.

Aspergillus nidulanstranslationally controlled tumor protein has a role in the balance between asexual and sexual differentiation and normal hyphal branching

Translationally controlled tumor protein (TCTP) is a highly conserved and ubiquitously expressed protein present in all eukaryotes. Cellular functions of TCTP include growth promoting, allergic response and responses to various cellular stresses, but the functions in filamentous fungi have not been reported. In this report, we characterized an Aspergillus nidulans TCTP (TcpA) with high similarity to TCTP. The level of tcpa mRNA was relatively high, both during vegetative growth stage and at early phases of development. TcpA was found predominantly in the nucleus during germination and mycelial growth, and was localized in cytoplasm and nuclei of vesicles on stipes during conidia development. Deletion of tcpA resulted in abnormal hyphal branch formation during vegetative growth. The tcpA deletion inhibited sexual development, but enhanced asexual development via induction of brlA expression. These results imply that TcpA is involved in normal hyphal branch establishment during vegetative growth and also has a role in the balance between asexual and sexual differentiation.

Targeting TCTP as a New Therapeutic Strategy in Castration-resistant Prostate Cancer

Heat shock protein 27 (Hsp27) is highly overexpressed in castration-resistant prostate cancer (CRPC) and an antisense inhibitor (OGX-427) is currently in phase II clinical trials. In order to understand mechanisms of action of Hsp27 and find new therapeutic targets specific of CRPC, we screened for Hsp27 client proteins. Here, we report that translationally controlled tumor protein (TCTP) is a new Hsp27 client protein involved in Hsp27 cytoprotection. We found that TCTP expression is absent or weak in normal prostate cells, moderately expressed in 18.5% of treatment naive PC, and becomes uniformly and strongly expressed in 75% of CRPC. To define TCTP function, we developed and worldwide patented a TCTP antisense oligonucleotide (ASO). Interestingly, we found that CRPC progression correlates with TCTP overexpression and loss of P53. TCTP knockdown restored P53 expression and function, suggesting that castration-sensitivity is directly linked to P53 expression. Collectively, these findings provide a new Hsp27 cytoprotection mechanism in CRPC, and preclinical proof-of-concept that combining ASO-mediated TCTP knockdown with castration and/or docetaxel therapy could serve as a novel strategy to treat CRPC, with no or little toxicity for normal prostate cells.

Molecular interaction of artemisinin with translationally controlled tumor protein (TCTP) of Plasmodium falciparum

Malaria causes millions of death cases per year. Since Plasmodium falciparum rapidly develops drug resistance, it is of high importance to investigate potential drug targets which may lead to novel rational therapy approaches. Here we report on the interaction of translationally controlled tumor protein of P. falciparum (PfTCTP) with the anti-malarial drug artemisinin. Furthermore, we investigated the crystal structure of PfTCTP. Using mass spectrometry, bioinformatic approaches and surface plasmon resonance spectroscopy, we identified novel binding sites of artemisinin which are in direct neighborhood to amino acids 19–46, 108–134 and 140–163. The regions covered by these residues are known to be functionally important for TCTP function. We conclude that interaction of artemisinin with TCTP may be at least in part explain the antimalarial activity of artemisinin.