Biochemical characterisation of TCTP questions its function as a guanine nucleotide exchange factor for Rheb

Rehmann, Holger; Bruning, Marc; Berghaus, Carsten; Schwarten, Melanie; Köhler, Katja; Stocker, Hugo; Stoll, Raphael; Zwartkruis, Fried; Wittinghofer, Alfred

doi:10.1016/j.febslet.2008.07.057

Cited by 77 publications

(63 citation statements)

References 28 publications

(42 reference statements)

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“…Thus, the idea that TCTP acts as a GEF for Rheb appeared attractive, but it remains controversial, since later studies failed to support the results described for Drosophila: We found that reducing TCTP levels did not reproducibly affect mTORC1 signalling in human cells, and we were unable to detect a stable interaction between TCTP and Rheb (Wang et al 2008). Similarly, Rehmann and colleagues did not detect GEF activity of TCTP for Rheb or any interaction between TCTP and Rheb (Rehmann et al 2008). …”

Section: Tctp and Cell Growth Regulationmentioning

confidence: 57%

“…Also, Hsu et al described TCTP in Drosophila as an activator of the small GTPase Rheb, an upstream activator of the mTORC1 pathway, and based on this, implicated TCTP in growth regulation (Hsu et al 2007). However, other follow-up studies could not confirm some of the findings in mammalian cells (Wang et al 2008;Rehmann et al 2008). Thus, while some studies indicate that TCTP could act as a growth-regulatory protein, these ideas and the mechanisms involved need further consolidation.…”

Section: Mechanistic Involvement In Cancer Progressionmentioning

confidence: 89%

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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: Tctp and Cell Growth Regulationmentioning

confidence: 57%

Section: Mechanistic Involvement In Cancer Progressionmentioning

confidence: 89%

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

Bommer

2017

Results and Problems in Cell Differentiation

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“…This observation is consistent with the demonstration that TCTP overexpression in mice results in systemic hypertension (Kim et al, 2008b); (2) TCTP interacts with protein synthesis elongation factor eEF1A and negatively regulates the guanosine-nucleotide-exchange reaction on eEF1A (Cans et al, 2003); (3) a study using gene knockdown in Drosophila reported the activity of TCTP as a guanine-nucleotide-exchange factor for the small GTPase, Rheb, and indicated involvement of TCTP in the target of rapamycin (TOR) signalling pathway (Hsu et al, 2007); however, recent results from our own (Wang et al, 2008) and two other laboratories (Chen et al, 2007;Rehmann et al, 2008) are not compatible with this conclusion.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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“…Moreover, overexpression of TCTP did not rescue mTORC1 signalling in amino acid-starved cells, and no stable interaction between TCTP and Rheb or mTORC1 was observed. Similarly, Rehmann et al [67] were unable to detect GDP exchange activity of TCTP towards Rheb. TCTP depletion in cells did not affect direct downstream targets of Rheb, and no interaction between TCTP and Rheb could be detected by NMR spectroscopy.…”

Section: Involvement Of Tctp With Growth Regulation and The Translatimentioning

confidence: 99%

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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Biochemical characterisation of TCTP questions its function as a guanine nucleotide exchange factor for Rheb

Cited by 77 publications

References 28 publications

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

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

Cellular Function and Regulation of the Translationally Controlled Tumour Protein TCTP

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