Dimerized, Not Monomeric, Translationally Controlled Tumor Protein Induces Basophil Activation and Mast Cell Degranulation in Chronic Urticaria

Translationally controlled tumor protein (TCTP) is also known as histamine releasing factor as it has the ability to activate mast cells. To investigate the role of TCTP in the pathogenesis of chronic spontaneous urticaria (CSU), we evaluated serum level of TCTP and effect of TCTP on basophil and mast cell degranulation. TCTP levels in the sera from 116 CSU patients and 70 normal healthy controls (NCs) were measured by ELISA. CD203c expression on basophils from CSU patients and β-hexosaminidase release from Laboratory of Allergic Disease 2 mast cells were measured upon stimulation monomeric and dimeric TCTP. Non-reducing Western blot analysis was used for detecting dimeric TCTP. No difference was observed in serum TCTP levels between CSU patients and NCs (p=0.676). However, dimeric TCTP intensity on Western blot was stronger in CSU patients than in NCs. TCTP levels were higher in patients with severe CSU (p=0.049) and with IgG positivity to FcɛRIα (p=0.038). A significant positive correlation was observed between TCTP and eosinophil cationic protein levels (Spearman's rho=0.341; p=0.001). Both basophil and mast cell degranulation were significantly increased after stimulation with dimeric TCTP, but not with monomic TCTP. The ability of TCTP to activate basophil and mast cells is dependent on dimerization, suggesting that the inhibition of TCTP dimerization can be a therapeutic option for CSU. Association between TCTP levels and the presence of IgG to high affinity Fc epsilon receptor I alpha subunit in CSU patients indicates that autoimmune mechanisms may be involved in the dimerization of TCTP.

Immunohistochemical Localization of Translationally Controlled Tumor Protein in Axon Terminals of Mouse Hippocampal Neurons

Translationally controlled tumor protein (TCTP) is a cytosolic protein with microtubule stabilization and calcium-binding activities. TCTP is expressed in most organs including the nervous system. However, detailed distribution and functional significance of TCTP in the brain remain unexplored. In this study, we investigated the global and subcellular distributions of TCTP in the mouse brain. Immunohistochemical analyses with anti-TCTP revealed that TCTP was widely distributed in almost all regions of the brain including the cerebral cortex, thalamus, hypothalamus, hippocampus, and amygdala, wherein it was localized in axon tracts and axon terminals. In the hippocampus, TCTP was prominently localized to axon terminals of the perforant path in the dentate gyrus, the mossy fibers in the cornu ammonis (CA)3 region, and the Schaffer collaterals in the CA1 field, but not in cell bodies of granule cells and pyramidal neurons, and in their dendritic processes. Widespread distribution of TCTP in axon tracts and axon terminals throughout the brain suggests that TCTP is likely involved in neurotransmitter release and/or maintaining synaptic structures in the brain, and that it might have a role in maintaining synaptic functions and synaptic configurations important for normal cognitive, stress and emotional functions.

Molecular mechanism and application of translationally controlled tumor protein in tumor targeting ;therapy / 国际肿瘤学杂志

Translationally controlled tumor protein (TCTP)is a small protein highly conserved in a variety of eukaryotic species.TCTP is overexpressed in various tumor cells and has been implicated in the regu-lation of cellular processes including apoptosis,DNA repair and drug resistance.By reviewing the recent pro-gress of TCTP research,TCTP is becoming an important regulator of DNA repair and a new molecular target for tumor therapy.

Expression of Translationally Controlled Tumor Protein (TCTP) Gene of Dirofilaria immitis Guided by Transcriptomic Screening

Dirofilaria immitis (heartworm) infections affect domestic dogs, cats, and various wild mammals with increasing incidence in temperate and tropical areas. More sensitive antibody detection methodologies are required to diagnose asymptomatic dirofilariasis with low worm burdens. Applying current transcriptomic technologies would be useful to discover potential diagnostic markers for D. immitis infection. A filarial homologue of the mammalian translationally controlled tumor protein (TCTP) was initially identified by screening the assembled transcriptome of D. immitis (DiTCTP). A BLAST analysis suggested that the DiTCTP gene shared the highest similarity with TCTP from Loa loa at protein level (97%). A histidine-tagged recombinant DiTCTP protein (rDiTCTP) of 40 kDa expressed in Escherichia coli BL21 (DE3) showed immunoreactivity with serum from a dog experimentally infected with heartworms. Localization studies illustrated the ubiquitous presence of rDiTCTP protein in the lateral hypodermal chords, dorsal hypodermal chord, muscle, intestine, and uterus in female adult worms. Further studies on D. immitis-derived TCTP are warranted to assess whether this filarial protein could be used for a diagnostic purpose.

Bioinformatic analysis for structure and function of TCTP from Spirometra mansoni

OBJECTIVE@#To 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.@*METHODS@#Open 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.@*RESULTS@#The 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.@*CONCLUSIONS@#Sm TCTP was a variety of biological functions of protein that may be used as a vaccine candidate molecule and drug target.

Advance in relationship between translationally controlled tumor protein and tumor / 国际外科学杂志

Translationally controlled tumor protein(TCTP)is a highly conserved and homologous protein that is widely expressed in all eukaryotic organisms and regulated at both the transcriptional and the translational level. TCTP participates in the regadation of cell cycle and proliferation, anti-apoptosis, and tumor reversion in tumor; it also correlates with ehemo-resistance. It may become potential targets of anti-tumor therapy and tumor reversion and provides a novel ideal for cancer therapy.