Roles of the translationally controlled tumour protein (TCTP) and the double-stranded RNA-dependent protein kinase, PKR, in cellular stress responses

Bommer, Ulrich‐Axel; Heng, Cheryl; Perrin, Aline; Dash, Philip R.; Lobov, Sergei; Elia, Androulla; Clemens, Michael J.

doi:10.1038/onc.2009.380

Cited by 39 publications

(33 citation statements)

References 58 publications

(93 reference statements)

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“…We have also demonstrated that TCTP mRNA translation is indeed inhibited by PKR in cell stress conditions, as, e.g. in serum starvation (Bommer et al 2002) or under calcium stress (Bommer et al 2010).…”

Section: Translational Regulation Of Tctp Synthesismentioning

confidence: 54%

“…Conversely, down-regulation of anti-apoptotic proteins forms part of the armory of p53 to promote apoptosis. Indeed down-regulation of TCTP through activation of a (temperature-sensitive) mutant protein of p53 (Tuynder et al 2002;Bommer et al 2010) was an initial observation in this context. The mutual antagonism between p53 and TCTP was then described by three groups in brief succession (Amson et al 2012;Chen et al 2011;Rho et al 2011).…”

Section: Stress Responsementioning

confidence: 99%

“…TCTP/fortilin has been reported to act as Ca 2+ -scavenger, and this was proposed as a yet another mechanism of its antiapoptotic activity (Graidist et al 2007). Indeed, overexpression of TCTP has been shown to protect cells against Ca 2+ -dependent apoptosis induced by thapsigargin (Graidist et al 2007;Bommer et al 2010), a reagent that inhibits the Ca 2+ -pump of the ER membrane, resulting in a significant increase in cytosolic Ca 2+ -levels. The notion of TCTP acting as a Ca 2+ -scavenger, or more generally as a 'buffer-like' molecule for Ca 2+ , is consistent with its high abundance and with the fact that its binding site is rather weak (Lucas et al 2014).…”

Section: Involvement In Cellular Stress Responsesmentioning

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: Translational Regulation Of Tctp Synthesismentioning

confidence: 54%

Section: Stress Responsementioning

confidence: 99%

Section: Involvement In Cellular Stress Responsesmentioning

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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“…It is not surprising, that activation of p53, one of the most powerful proapoptotic proteins, down-regulates the anti-apoptotic protein TCTP. Such observations have been made earlier, using a temperature sensitive mutant of p53, in two quite different cellular systems [42,56]. Several recent studies now describe TCTP as an interaction partner and antagonist for p53, albeit by differing mechanisms.…”

Section: + -Atpasementioning

confidence: 65%

“…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: 93%

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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The Translationally Controlled Tumor Protein and the Cellular Response to Ionizing Radiation-Induced DNA Damage

Zhang

Shim

Toledo

et al. 2017

Results and Problems in Cell Differentiation

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The absorption of ionizing radiation by living cells can directly disrupt atomic structures, producing chemical and biological changes. It can also act indirectly through radiolysis of water, thereby generating reactive chemical species that may damage nucleic acids, proteins, and lipids. Together, the direct and indirect effects of radiation initiate a series of biochemical and molecular signaling events that may repair the damage or culminate in permanent physiological changes or cell death. In efforts to gain insight into the mechanisms underlying these effects, we observed a prominent upregulation of the Translationally Controlled Tumor Protein (TCTP) in low dose/low dose rate Cs γ-irradiated cells that was associated with adaptive responses that reduced chromosomal damage to a level lower than what occurs spontaneously. Therefore, TCTP may support the survival and genomic integrity of irradiated cells through a role in the DNA damage response. Consistent with this postulate, TCTP was shown to physically interact with ATM, an early sensor of DNA damage, and to exist in a complex with γH2A.X, in agreement with its distinct localization with the foci of the DNA damage marker proteins γH2A.X, 53BP1, and P-ATM. Cells lacking TCTP failed to repair chromosomal damage induced by γ-rays. Further, TCTP was shown to interact with the DNA-binding subunits, Ku70 and Ku80, of DNA-PK, a major participant in nonhomologous end joining of DNA double strand breaks. Moreover, TCTP physically interacted with p53, and its knockdown attenuated the radiation-induced G delay, but prolonged the G delay. Here, we briefly review the biochemical events leading to DNA damage by ionizing radiation and to its sensing and repair, and highlight TCTP's critical role in maintaining genomic integrity in response to DNA-damaging agents.

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Roles of the translationally controlled tumour protein (TCTP) and the double-stranded RNA-dependent protein kinase, PKR, in cellular stress responses

Cited by 39 publications

References 58 publications

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

Cellular Function and Regulation of the Translationally Controlled Tumour Protein TCTP

The Translationally Controlled Tumor Protein and the Cellular Response to Ionizing Radiation-Induced DNA Damage

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