Disease relevance of TPT1

• Furthermore, the antisense depletion of fortilin from breast cancer cell line MCF-7 was associated with massive cell death [1].
• Recombinant TCTP protein purified from an Escherichia coli expression system inhibited purified HeLa cell plasma membrane Na,K-ATPase in a dose-dependent manner [2].
• Immunocytochemistry using HeLa cells transiently expressing FLAG-tagged fortilin and immunohistochemistry using human breast ductal carcinoma tissue and anti-fortilin antibody both showed that fortilin is predominantly localized in the nucleus [1].
• TCTP was found in several healthy and tumoral cells including erythrocytes, hepatocytes, macrophages, platelets, keratinocytes, erythroleukemia cells, gliomas, melanomas, hepatoblastomas, and lymphomas [3].
• CONCLUSIONS: The results of the present study demonstrate, for the first time, the expression of TCTP in the human prostate and in prostate cancer cells, and suggest the involvement of the protein in key-processes such as apoptosis, cellular differentiation, and in the control of sperm functions [4].

Psychiatry related information on TPT1

• Decreased brain histamine-releasing factor protein in patients with Down syndrome and Alzheimer's disease [5].

High impact information on TPT1

• Spontaneous release of histamine from basophils and histamine-releasing factor in patients with atopic dermatitis and food hypersensitivity [6].
• The histamine-releasing factor was found to activate basophils through surface-bound IgE [6].
• Mononuclear cells from persons with food allergies spontaneously produced a histamine-releasing factor in vitro that provoked the release of histamine from the basophils of other food-sensitive persons, but not from those of normal controls [6].
• Molecular chaperone machines: chaperone activities of the cyclophilin Cyp-40 and the steroid aporeceptor-associated protein p23 [7].
• An immunoglobulin E (IgE)-dependent histamine-releasing factor (HRF) produced by lymphocytes of atopic children and present in biological fluids of allergic patients has been identified and purified [8].

Chemical compound and disease context of TPT1

• We conclude that in patients with food hypersensitivity, exposure to the relevant antigens produces a cytokine (histamine-releasing factor) that interacts with IgE bound to the surface of basophils, causing them to release histamine [6].
• Some patients with large-cell anaplastic lymphoma (Ki 1 lymphoma) have the translocation t(2;5) (p23; q35), involving a possible growth-regulating tyrosine kinase [9].
• Using quantitative biochemical, immunochemical and morphological methods, we demonstrate that inhibitors of the cystine protease, L3/p23, located inside the capsid block the degradation of the capsid-stabilizing protein VI, and prevent virus uncoating at the nuclear membrane [10].
• We directly expressed human R-ras 23,000-dalton protein (p23) cDNA in Escherichia coli under the control of the trp promoter [11].
• On the other hand, the association between endometriosis and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) exposure has been discussed in recent years, and our previous results revealed that IgE-dependent histamine-releasing factor (HRF) is inducible by TCDD [12].

Biological context of TPT1

• Recombinant placental TPT1 bound calcium in vitro, while downregulation of the protein levels by siRNA in HTR-8/SVneo cells was associated with a reduced cellular calcium-uptake activity and buffering capacity [13].
• The present study aimed to evaluate the expression of TPT1 in the human placenta and to examine the functional role of the protein in the calcium binding and homeostasis of trophoblast cells [13].
• TPT1 expression significantly increased during gestation, with the higher protein and mRNA levels reached at term [13].
• TPT1 protein and mRNA were detected in first-trimester and term placenta [13].
• Inhibition of TCTP expression by anti-sense cDNA or small interfering RNA molecules results in suppression of the malignant phenotype and in cellular reorganization, similar to the effect of SIAH-1 [14].

Anatomical context of TPT1

• The effect of TPT1 knockdown by small interfering RNA (siRNA) on calcium uptake and buffering was assessed in the HTR-8/SVneo cell line [13].
• In the tissue, TPT1 was localized in the villous trophoblast [13].
• Here we show that TCTP secretion was insensitive to either brefeldin A or monensin, suggesting that it proceeds via an endoplasmic reticulum/Golgi-independent or nonclassical pathway [15].
• Fortilin, like MCL1, was rapidly inducible in serum-stimulated human aortic vascular smooth muscle cells [16].
• We conclude that HrHRF, in addition to functioning as a histamine-releasing factor, can differentially modulate the secretion of cytokines from human basophils, eosinophils, T cells, and murine B cells, suggesting that it may induce a complex array of responses at sites of allergic inflammation [17].

Associations of TPT1 with chemical compounds

• Translationally controlled tumor protein acts as a guanine nucleotide dissociation inhibitor on the translation elongation factor eEF1A [18].
• TCTP (also called histamine-releasing factor) has been described previously as a secreted protein that participates in inflammatory responses by promoting the release of histamine [15].
• Antiapoptotic protein partners fortilin and MCL1 independently protect cells from 5-fluorouracil-induced cytotoxicity [19].
• Secondary structure predictions and gel electrophoretic mobility investigations on P23/TCTP transcripts confirmed the potential of this mRNA to form extensive secondary structure [20].
• Plk phosphorylates TCTP on two serine residues in vitro and cofractionates with the majority of kinase activity toward TCTP in mitotic cell lysates [21].
• A crystal structure of the E12V mutant hTCTP, which lacks the guanine nucleotide exchange factor activity, shows that the deficiency appears to be caused by loss of a salt-bridging interaction with Lys-45 of hRheb [22].

Physical interactions of TPT1

• In vitro and in vivo studies confirmed that TCTP bound specifically eEF1Bbeta and eEF1A [18].
• Fortilin specifically interacted with MCL1 both in vitro and in vivo [16].
• We screened a rat skeletal muscle cDNA library using yeast two-hybrid system and found that TCTP interacts with the third large cytoplasmic domain of alpha1 as well as alpha2 isoforms of Na,K-ATPase, believed involved in the regulation of Na,K-ATPase activity [2].

Regulatory relationships of TPT1

• To elucidate novel functions of HRF p23 in airway inflammation, we examined the effects of human recombinant HRF p23 (hrHRF) on bronchial epithelium and found that hrHRF stimulated the secretions of IL-8 and granulocyte/macrophage colony-stimulating factor by both primary cultures of human bronchial epithelial cells and BEAS-2B cells [23].
• Monocyte chemotactic and activating factor is a potent histamine-releasing factor for human basophils [24].
• An immunoglobulin E-dependent recombinant histamine-releasing factor induces interleukin-4 secretion from human basophils [25].
• Recombinant histamine-releasing factor enhances IgE-dependent IL-4 and IL-13 secretion by human basophils [26].

Other interactions of TPT1

• Identification of the interaction between the human recombinant histamine releasing factor/translationally controlled tumor protein and elongation factor-1 delta (also known as eElongation factor-1B beta) [27].
• Additionally, MS analysis also identified eEF1A as a TCTP interactor [18].
• H2O2, but not IL-1 beta or tumor necrosis factor-alpha, stimulated secretion of HRF p23 by BEAS-2B cells, suggesting that oxidative stress may trigger the release of HRF p23 from bronchial epithelial cells [23].
• OBJECTIVE: This study was conducted to analyze the contribution of chemokines, such as monocyte chemotactic protein-1 (IgE-independent), to improve the detection of IgE-dependent histamine-releasing factor [28].
• The observed proteins included unexpected proteins such as Sox5, two isoforms of Rab14, Rab3A, translationally controlled tumor protein, and one protein of previously unknown function [29].

Analytical, diagnostic and therapeutic context of TPT1

• Additionally, DNA microarray data classifies TCTP (HrHRF) as co-regulated with ribosomal proteins and recent structural analysis of TCTP (HrHRF) relates it to a guanine nucleotide-free chaperone [27].
• The intracellular localization of fortilin was predominantly nuclear and identical to that of MCL1, as shown by immunostaining and confocal microscopy analysis [16].
• Western blot analysis using anti-fortilin antibody showed more extensive expression in cancerous cell lines (H1299, MCF-7, and A549) than in cell lines derived from normal tissue (HEK293) [1].
• Sequence analysis of fortilin revealed it to be a 172-amino acid polypeptide highly conserved from mammals to plants [1].
• Northern blot analysis showed the fortilin message to be ubiquitous in normal tissue but especially abundant in the liver, kidney, and small intestine [1].

References