Translationally controlled tumour protein (TCTP) is a novel glucose-regulated protein that is important for survival of pancreatic beta cells

Diraison, Frédérique; Hayward, Katy; Sanders, Kelly; Brozzi, Flora; Lajus, Sophie; Hancock, John T.; Francis, JE; Ainscow, Edward; Bommer, Ulrich‐Axel; Molnár, Elek; Avent, ND; Váradi, Anikó

doi:10.1007/s00125-010-1958-7

Cited by 45 publications

(34 citation statements)

References 49 publications

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“…Interestingly, this paper also reports that glucose deprivation resulted in down-regulation of TCTP, followed by cell death. The latter finding is corroborated by our recent study on pancreatic beta-cells, showing that an exposure to high glucose (25 mM) leads to an increase in intracellular TCTP levels [43]. This paper also demonstrated that overexpression of TCTP partially protects beta-cells against the induction of apoptosis by high levels of saturated fatty acids (palmitate), a particular stress situation for these cells.…”

Section: + -Atpasesupporting

confidence: 82%

“…However, it is likely that this treatment merely reflects a stress condition rather that a genuine nutritional signal. Our recent study on pancreatic beta-cells demonstrated that TCTP levels are subject to glucose regulation in this cell type [43].…”

Section: Cell Physiological Conditions Resulting In Regulation Of Tctmentioning

confidence: 92%

“…Several groups reported regulation of TCTP levels under Ca ++ -stress conditions [42][43][44], and overexpression of TCTP partially protected cells from induction of apoptosis by Ca ++ -stress [12,42]. The importance of TCTP as a survival factor, involved in the development of cellular resistance against anticancer drugs was demonstrated earlier for etoposide [7] and 5-fluorouracil [45].…”

Section: + -Atpasementioning

confidence: 88%

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Cellular Function and Regulation of the Translationally Controlled Tumour Protein TCTP

Bommer¹

2012

TOALLJ

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Abstract:The 'translationally controlled tumour protein' TCTP was originally discovered 30 years ago by researchers interested in proteins regulated at the translational level. Cloning and sequencing confirmed the conservation of this protein among all eukaryotic kingdoms, but did not reveal any functional clue, and TCTP was listed in the databases as a 'family' of its own. The functional characterisation of this protein extended over more than a decade, leading to a plethora of individual functions and interactions that have been ascribed to this protein. A major addition to the functional characterisation of TCTP was the identification in 1995 of its histamine releasing factor (HRF) activity in allergic conditions, which for the first time described an extracellular activity for TCTP in human disease. This triggered a host of additional publications aimed at characterising this HRF activity, which are discussed in other articles of this issue. Another milestone in the elucidation of TCTP's function was the demonstration of its anti-apoptotic activity in 2001. Evidence is also accumulating for a role of TCTP in the cell cycle and in early development. This article provides an overview of the main cellular activities of TCTP. The second part will summarise our current knowledge on the mechanisms involved in regulating intracellular TCTP levels.

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Section: + -Atpasesupporting

confidence: 82%

Section: Cell Physiological Conditions Resulting In Regulation Of Tctmentioning

confidence: 92%

Section: + -Atpasementioning

confidence: 88%

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Cellular Function and Regulation of the Translationally Controlled Tumour Protein TCTP

Bommer¹

2012

TOALLJ

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“…Overexpression of TCTP prevented cell death induced by palmitate (Diraison et al 2011). These results imply that TCTP protects β-cells against stress induced by hyperglycaemia and by high concentrations of fatty acids.…”

Section: Metabolic Regulation and Diabetesmentioning

confidence: 53%

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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“…Furthermore, TCTP ablation arrested cell-cycle progression at the G 1 phase in human pancreatic cancer cells, similar to when the cells were depleted of Pim-3. Diraison and colleagues recently reported that increased TCTP expression reduced the sensitivity of pancreatic b cells to apoptosis (51). We previously observed that Pim-3 shRNA treatment in vitro enhanced the apoptosis of various types of cancer cells (3)(4)(5).…”

Section: Discussionmentioning

confidence: 77%

A Novel Regulatory Mechanism of Pim-3 Kinase Stability and Its Involvement in Pancreatic Cancer Progression

Zhang

Liu

Wang

et al. 2013

Molecular Cancer Research

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Translationally controlled tumor protein (TCTP/TPT1) was identified from a yeast 2-hybrid screen and shown to interact with Pim-3, a member of the proto-oncogene Pim family with serine/threonine kinase activity. TCTP was aberrantly expressed in human pancreatic cancer cells and malignant ductal epithelial cells, but not in normal pancreatic duct epithelial cells adjacent to tumor foci of human pancreatic cancer tissue. Moreover, TCTP colocalized with Pim-3 both in human pancreatic cancer cells and in clinical tissues. Mapping studies revealed that the interaction between Pim-3 and TCTP occurred through the C-terminal region of Pim-3 and N-terminal region of TCTP. Although Pim-3 had no effect on TCTP expression or phosphorylation, overexpression of TCTP increased the amount of Pim-3 in a dose-dependent manner. Interestingly, RNAi-mediated ablation of TCTP expression reduced Pim-3 protein but not mRNA, through a mechanism involving the ubiquitin-proteasome degradation system. As a consequence of Pim-3 instability and subsequent degradation, tumor growth in vitro and in vivo was inhibited by arresting cell-cycle progression and enhancing apoptosis. Furthermore, TCTP and Pim-3 expression were significantly correlated in pancreatic adenocarcinoma specimens, and patients with highly expressed TCTP and Pim-3 presented with a more advanced tumor stage. These observations indicate that TCTP enhances Pim-3 stability to simultaneously promote and prevent cell-cycle progression and apoptosis, respectively. Hence, TCTP and Pim-3 serve a pivotal role in human pancreatic cancer with important ramifications for clinical diagnostic and therapeutic implications.

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Translationally controlled tumour protein (TCTP) is a novel glucose-regulated protein that is important for survival of pancreatic beta cells

Cited by 45 publications

References 49 publications

Cellular Function and Regulation of the Translationally Controlled Tumour Protein TCTP

Cellular Function and Regulation of the Translationally Controlled Tumour Protein TCTP

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

A Novel Regulatory Mechanism of Pim-3 Kinase Stability and Its Involvement in Pancreatic Cancer Progression

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