Expression of the gene and processed pseudogenes encoding the human and rabbit translationally controlled tumour protein (TCTP)

Thiele, Holger; Berger, Mario; Skalweit, Angela; Thiele, B

doi:10.1046/j.1432-1327.2000.01609.x

Cited by 85 publications

(95 citation statements)

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“…The yeast orthologue of TCTP was named 'microtubule and mitochondria interacting protein' (Mmi1p) (Rinnerthaler et al 2006), but in another paper, it was also identified as the 'translation-machinery-associated protein 19' (TMA19) (Fleischer et al 2006), and yet the gene symbol in yeast is YKL056c. In contrast, the gene symbol in higher eukaryotes is TPT1, for 'tumour protein, translationally controlled-1' (Thiele et al 2000).…”

Section: The 'Translationally Controlled Tumour Protein Tctp': Names mentioning

confidence: 99%

“…Several of these pseudogenes have been studied in some detail in the rabbit (Thiele et al 2000) and in mouse (Fiucci et al 2003), and only few were found to have the potential to produce a protein product.…”

Section: Gene Structure and Mrnamentioning

confidence: 99%

“…Northern blot analysis of TCTP mRNAs from a range of different tissues revealed that all cells produce two different TCTP mRNA species in both rabbits (Thiele et al 2000) and in humans (Andree et al 2006), the longer one bearing a 320 nucleotide extension at the 3 0 -end, which is generated by an additional polyadenylation site. These two isoforms comprise a total of about 800 and 1200 nucleotides, respectively (Andree et al 2006).…”

Section: Gene Structure and Mrnamentioning

confidence: 99%

“…These two isoforms comprise a total of about 800 and 1200 nucleotides, respectively (Andree et al 2006). The ratio between the two mRNA species differs considerably between different tissues, but the short mRNA is always in excess (Thiele et al 2000). The importance for the production of these two different mRNA species has not yet been elucidated, but interestingly, in mouse tissues, there was only one TCTP mRNA isoform detected (Fiucci et al 2003).…”

Section: Gene Structure and Mrnamentioning

confidence: 99%

“…Mammalian TCTP mRNAs contain an open reading frame of 519 nt (172 amino acids), a 5 0 -UTR of about 100 nt and a 3 0 -UTR of about 200 nt or of 520 nt for the longer isoform (Thiele et al 2000). A particular feature of TCTP mRNAs, indicative for translational regulation, is a 5 0 -terminal oligopyrimidine tract (5 0 -TOP): sequence 5 0 -CTTTTCCG .…”

Section: Gene Structure and Mrnamentioning

confidence: 99%

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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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Section: The 'Translationally Controlled Tumour Protein Tctp': Names mentioning

confidence: 99%

Section: Gene Structure and Mrnamentioning

confidence: 99%

Section: Gene Structure and Mrnamentioning

confidence: 99%

Section: Gene Structure and Mrnamentioning

confidence: 99%

Section: Gene Structure and Mrnamentioning

confidence: 99%

See 3 more Smart Citations

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

Bommer

2017

Results and Problems in Cell Differentiation

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Cellular distribution of translationally controlled tumor protein in rat and human testes

et al. 2001

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In a recent proteomic study we identified 53 spermatogonial proteins among which was the translationally controlled tumor protein (TCTP). This is a protein previously reported as being implicated in proliferation events in normal and tumoral tissues that had never previously been seen in the testis. The present study was aimed at establishing the complete cellular distribution of TCTP and its transcript and the ontogenetic expression of this gene within the testis. Using an immunohistochemistry technique, an intense TCTP signal was detected in gonocytes (the prespermatogonia) in the fetal rat testis and in spermatogonia within adult human and neonatal and adult rat testes. Meiotic spermatocytes and postmeiotic haploid spermatids were also strongly immunostained in a stage-dependent manner in human and rat testes. In addition, different levels of TCTP expression were also observed in the testicular somatic cells, with strong expression in Leydig cells and peritubular cells, and weak expression in Sertoli cells. Western and Northern blot analyses confirmed the presence of TCTP at all ages studied, with higher levels of RNA expression at 9 and 20 d postpartum, when spermatogonia and primary spermatocytes represent the highest proportion of germ cells: it was also confirmed that TCTP is present in all populations of isolated testicular cells. A transcript of 0.85 kb corresponding to TCTP, was expressed at all ages studied. This transcript was found to be expressed strongly in spermatogonia, somewhat less in isolated Leydig, resident macrophage, peritubular and Sertoli cells, weakly in the primary spermatocytes but not at all in spermatids. Interestingly, in the latter, a different transcript of 1.1 kb was present. The same 1.1 kb transcript appeared in testis extracts from 35 days postpartum onwards, corresponding to an age when spermatids accumulate within the tubules. Of note is that resident macrophages were found to express both the 0.85 and the 1.1 kb transcripts. We conclude that the strong expression of TCTP in spermatogonia makes it highly likely that the protein plays a significant role in spermatogenesis.

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Relevance of Pseudogenes to Human Genetic Disease

Sen

2013

Encyclopedia of Life Sciences

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Pseudogenes, regarded as ‘plagiarised slip‐ups’ or ‘genomic fossils’, are the dysfunctional genomic copies lingering on in the genome for millions of years. The nonfunctional relics of their functional counterparts are now being recognised as genomic treasures presenting glimpses of the evolutionary chronicles of human genome. The recent flurry of experimental evidences indicating sequence conservation of the pseudogenes constructively regulating their functional homologues are now challenging their ‘junk DNA’ appearance. Pseudogenes are observed to harbour sequence variations that become degenerative disease‐causing mutations when transmitted to their colocalised progenitors through gene conversion event. The issue of pseudogene deregulation in several genetic diseases including cancer is now of the essence in the context of disease progression in humans. Different aspects of the involvement of pseudogenes and their relevance to human genetic disease are recaptured here. Key Concepts: A genetic disorder, which may or may not be heritable, is a disease caused by genomic or chromosomal aberrations. An inherited disease is a genetic disorder that is passed down from the parents' genes to that of the offspring. For example, some forms of cancer may be originated as an inherited genetic condition in some people. Duplicated pseudogenes arise due to unequal crossing over between two homologous chromosomes (during the process of DNA replication) followed by nondeleterious mutations. Processed pseudogenes, often termed as ‘dead on arrival’, are ensued by reverse transcription of mature mRNAs and reinclusion of the cDNAs into the genome. Pseudogenes may interfere with factors regulating the mRNA stability; provide mechanistic linkage between their expression and disease formation and thus anomalous pseudogene expression can be indicative of different physiological conditions, including diseases like diabetes and cancer. Gene conversion involves the unidirectional transfer of genetic material from a ‘donor’ sequence (intact homologous sequence) to a highly homologous ‘acceptor’ containing the ‘double strand break’ and can occur between sister chromatids, homologous chromosomes or homologous sequences on either the same chromatid or different chromosomes. Pseudogenes that are colocalised with their progenitors were seen to be the potential candidates of gene conversion event and thus the sequence variations accumulated in pseudogenes turn out to be disease‐causing mutations when they are transferred to other genes rendering them nonfunctional. Some pseudogenes were observed to post‐transcriptionally regulate their parental genes by three distinct mechanisms: (1) suppression of gene expression by natural antisense RNA; (2) RNA interference by producing siRNAs and (3) act as miRNA decoys. Pseudogenes can partially retain or totally resurrect their original functions. Being the paradigm of neutral evolution pseudogenes provide snapshots of the evolutionary history of the human genome. The neutral characteristic of all pseudogenic regions renders them relevant to determine the nature of neutral sequence evolution among different regions in the genome.

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Expression of the gene and processed pseudogenes encoding the human and rabbit translationally controlled tumour protein (TCTP)

Cited by 85 publications

References 44 publications

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

Cellular distribution of translationally controlled tumor protein in rat and human testes

Relevance of Pseudogenes to Human Genetic Disease

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