cDNA sequence coding for a translationally controlled human tumor protein

Gross, B; Gaestel, Matthias; Böhm, H; Bielka, H

doi:10.1093/nar/17.20.8367

Cited by 119 publications

(71 citation statements)

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“…These data also suggest that the C-terminal region (102-172) of TCTP is essential for interaction with Na,K-ATPase ␣ subunit and is sufficient to reduce the Na,K-ATPase activity. DISCUSSION TCTP has been identified in the proliferative stage of breast tumor (25) and has been initially reported to be present in all normal cell types, with the exception of kidney cells (16). However, we detected endogenous TCTP in COS-7 cells and rat kidney tissue by Western blotting, 2 and it now appears that TCTP exists in all normal cell types.…”

Section: C-terminal Homology Region 2 Of Tctp (Residues 102-172) Is Ementioning

confidence: 54%

Translationally Controlled Tumor Protein Interacts with the Third Cytoplasmic Domain of Na,K-ATPase α Subunit and Inhibits the Pump Activity in HeLa Cells

Jung

Kim²,

Kim

et al. 2004

Journal of Biological Chemistry

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Translationally controlled tumor protein (TCTP) is a growth-related protein under transcriptional as well as translational control. 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 ␣1 as well as ␣2 isoforms of Na,K-ATPase, believed involved in the regulation of Na,K-ATPase activity. Interaction between TCTP and Na,K-ATPase was confirmed by coimmunoprecipitation in yeast and mammalian cells. We also showed, using 86 Rb ؉ uptake assay, that overexpression of TCTP inhibited Na,K-ATPase activity in HeLa cells. Northern and Western blotting studies of HeLa cells transiently transfected with GFPtagged TCTP showed that overexpression of TCTP did not change mRNA and protein levels of Na,K-ATPase. Recombinant TCTP protein purified from an Escherichia coli expression system inhibited purified HeLa cell plasma membrane Na,K-ATPase in a dose-dependent manner. Using deletion analysis, we also found that the C-terminal 102-172-amino-acid region of rat TCTP that contains the TCTP homology region 2 is essential for its association with, and inhibition of, Na,K-ATPase. Na,K-ATPase, a multimembrane-spanning enzyme, is essential for maintaining transmembrane gradients of Na ϩ and K ϩ ions and thus for cell homeostasis (1). These ionic gradients serve to control essential cellular processes such as cell volume, membrane potential, and nutrient transport (2). In addition, Na,K-ATPase is involved in cell proliferation and differentiation, heart and vascular muscle contraction, and neurotransmitter and hormone secretion (3). Thus dysfunction of this enzyme can profoundly affect cell function. Na,K-ATPase is composed of a catalytic 110-kDa ␣ subunit and a glycosylated 40 -60-kDa ␤ subunit. The ␣ subunit contains binding sites for cations, ATP, and cardiac glycosides. It has been suggested that there might exist a diffusible cytoplasmic regulator of Na,K-ATPase activity, possibly modulated by protein kinases and hormones (4, 5). The third large cytoplasmic domain (CD3) 1 of Na,K-ATPase was proposed to be one of the domains involved in the regulation of its activity by insulin, thereby playing an important role in the catalytic function and regulation of this enzyme (6). Interactions between the Nterminal region of the Na,K-ATPase ␣ subunit with phosphoinositide-3 kinase (7), cytoplasmic domain 2 (CD2) and CD3 with ankyrin (8, 9), CD3 with cofilin (10), and purified Na,KATPase with actin (11) and adducin (12) have also been demonstrated.We looked for other cytoplasmic agents that might interact with the CD3 of Na,K-ATPase ␣ subunit and regulate its activity and found that translationally controlled tumor protein (TCTP) acts as a cytoplasmic repressor of Na,K-ATPase. TCTP is a growth-related protein, under tight transcriptional as well as translational control (13,14). It occurs as a 23-kDa protein in humans and has a 21-kDa homologue in mice but shows no significant homology with any other family of proteins. Based on structural studies o...

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Section: C-terminal Homology Region 2 Of Tctp (Residues 102-172) Is Ementioning

confidence: 54%

Translationally Controlled Tumor Protein Interacts with the Third Cytoplasmic Domain of Na,K-ATPase α Subunit and Inhibits the Pump Activity in HeLa Cells

Jung

Kim²,

Kim

et al. 2004

Journal of Biological Chemistry

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“…Asp4 and Thr13 in Z46805 are Tyr4 and Met13 in our genomic sequence. The published human and mouse cDNA sequences [2,3] show a tyrosine residue at the position 4 (human and mouse) and a methionine residue (human) or a leucine residue (mouse) at the position 13. All our genomic sequences were confirmed by the sequences of two independent cDNAs and six pseudogenes which were identical in all discrepancies discussed.…”

Section: Discussionmentioning

confidence: 99%

“…The mouse protein was also designated as p21 [2] and the human homologue as p23 [3]. TCTP is a highly conserved fairly abundant protein which is found not only in mammals but also in many other species, including nematodes [4], trypanosomes [5], and plants [6].…”

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confidence: 99%

Structure of the promoter and complete sequence of the gene coding for the rabbit translationally controlled tumor protein (TCTP) P23

Thiele

Berger

Lenzner

et al. 1998

European Journal of Biochemistry

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We have isolated genomic recombinants containing the complete gene coding for the rabbit translationally controlled tumor protein (TCTP), also known as histamine-releasing factor (HRF) P23. The gene is organized into five introns and six exons and its total length amounts to 3819 nucleotides. All intron/ exon boundaries are in accordance with the GT/AG rule. Transcription of the gene generates two mRNAs of 843 and 1163 nucleotides differing in the length of their 3′-untranslated regions. They are formed by alternative polyadenylation. The transcription initiation site has been determined by comparison of sequences of the gene and several processed TCTP pseudogenes. The full-length 5′-untranslated region comprises 116 nucleotides and starts with an oligopyrimidine tract important for translational regulation. Additionally 1.2 kb of the 5′-flanking promoter region has been sequenced. The promoter contains a TATA box at Ϫ30 and potential binding sites for transcription factors such as stimulating protein 1 (Sp1), nuclear factor 1 (NF1), activator protein 1 (AP1), c-Ets1, cAMP-response element (CP2), myeloid-specific zinc finger protein 1 (MZF1) and others. For functional analysis 5′-flanking sequences up to Ϫ918 were fused to the chloramphenicol acetyltransferase (CAT) gene and tested using a rabbit aortic smoothmuscle cell line by cell transfection and CAT assays. The results confirm that the analyzed gene is the actively transcribed TCTP gene.Keywords : translationally controlled tumor protein; histamine-releasing factor; gene organization ; promoter; pseudogenes.The translationally controlled tumor protein (TCTP) was described initially by Brawerman's group [1] as a growth-related protein in mouse ascites and erythroleukemic cells whose mRNA is stored as translationally inactive mRNP complexes. The mouse protein was also designated as p21 [2] and the human homologue as p23 [3]. TCTP is a highly conserved fairly abundant protein which is found not only in mammals but also in many other species, including nematodes [4], trypanosomes [5], and plants [6]. Recent studies have shown that the term 'TCTP' is somewhat misleading because it is definitely not a protein restricted to tumor cells [7]. This situation is further complicated by experiments showing that TCTP can act on basophils of atopic patients in an IgE-dependent way as a histamine releasing factor [8]. Furthermore TCTP has been described as a protein which binds calcium with high affinity, but does not belong to any known family of calcium-binding proteins [5,9].Despite the fact that its physiological role is currently not clearly defined, the regulation of expression of TCTP demands Correspondence to B.-J. Thiele,

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“…This paper also names the different agents that trigger and regulate TCTP release, and it describes the underlying mechanisms for secretion in detail, which I will only briefly summarise here. First, the protein TCTP does not have a signal sequence (Chitpatima et al 1988;Gross et al 1989), and no precursor protein for TCTP was detected, meaning that TCTP is not secreted through the classical secretory pathway, via the ER and Golgi apparatus. This was confirmed by the finding that its secretion was insensitive to brefeldin A or monensin, two inhibitors of this pathway (Amzallag et al 2004).…”

Section: Tctp As Extracellular 'Signaling Molecule' In Immune Reactionsmentioning

confidence: 99%

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

Bommer

2017

Results and Problems in Cell Differentiation

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The Translational Controlled Tumour Protein TCTP (gene symbol TPT1, also called P21, P23, Q23, fortilin or histamine-releasing factor, HRF) is a highly conserved protein present in essentially all eukaryotic organisms and involved in many fundamental cell biological and disease processes. It was first discovered about 35 years ago, and it took an extended period of time for its multiple functions to be revealed, and even today we do not yet fully understand all the details. Having witnessed most of this history, in this chapter, I give a brief overview and review the current knowledge on the structure, biological functions, disease involvements and cellular regulation of this protein. TCTP is able to interact with a large number of other proteins and is therefore involved in many core cell biological processes, predominantly in the response to cellular stresses, such as oxidative stress, heat shock, genotoxic stress, imbalance of ion metabolism as well as other conditions. Mechanistically, TCTP acts as an anti-apoptotic protein, and it is involved in DNA-damage repair and in cellular autophagy. Thus, broadly speaking, TCTP can be considered a cytoprotective protein. In addition, TCTP facilitates cell division through stabilising the mitotic spindle and cell growth through modulating growth signalling pathways and through its interaction with the proteosynthetic machinery of the cell. Due to its activities, both as an anti-apoptotic protein and in promoting cell growth and division, TCTP is also essential in the early development of both animals and plants. Apart from its involvement in various biological processes at the cellular level, TCTP can also act as an extracellular protein and as such has been involved in modulating whole-body defence processes, namely in the mammalian immune system. Extracellular TCTP, typically in its dimerised form, is able to induce the release of cytokines and other signalling molecules from various types of immune cells. There are also several examples, where TCTP was shown to be involved in antiviral/antibacterial defence in lower animals. In plants, the protein appears to have a protective effect against phytotoxic stresses, such as flooding, draught, too high or low temperature, salt stress or exposure to heavy metals. The finding for the latter stress condition is corroborated by earlier reports that TCTP levels are considerably up-regulated upon exposure of earthworms to high levels of heavy metals. Given the involvement of TCTP in many biological processes aimed at maintaining cellular or whole-body homeostasis, it is not surprising that dysregulation of TCTP levels may promote a range of disease processes, foremost cancer. Indeed a large body of evidence now supports a role of TCTP in at least the most predominant types of human cancers. Typically, this can be ascribed to both the anti-apoptotic activity of the protein and to its function in promoting cell growth and division. However, TCTP also appears to be involved in the later stages of cancer progression, such ...

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cDNA sequence coding for a translationally controlled human tumor protein

Cited by 119 publications

References 2 publications

Translationally Controlled Tumor Protein Interacts with the Third Cytoplasmic Domain of Na,K-ATPase α Subunit and Inhibits the Pump Activity in HeLa Cells

Translationally Controlled Tumor Protein Interacts with the Third Cytoplasmic Domain of Na,K-ATPase α Subunit and Inhibits the Pump Activity in HeLa Cells

Structure of the promoter and complete sequence of the gene coding for the rabbit translationally controlled tumor protein (TCTP) P23

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

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