14-3-3 proteins regulate Tctp–Rheb interaction for organ growth in Drosophila

Le, Thao Phuong; Vuong, Linh Thuong; Kim, Ah-Ram; Hsu, Ya‐Chieh; Choi, Kwang‐Wook

doi:10.1038/ncomms11501

Cited by 42 publications

(49 citation statements)

References 52 publications

(83 reference statements)

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“…Consistent with this, reducing Drosophila TCTP levels reduced cell size, cell number and organ size, similar to Rheb mutant phenotypes. Subsequently, this group also reported that the 14-3-3 proteins regulate the interaction between TCTP and Rheb, thus playing an important role in regulating organ growth in Drosophila (Le et al 2016). The TCTP-Rheb interaction was further confirmed for the human proteins by molecular modelling studies (Dong et al 2009).…”

Section: Tctp and Cell Growth Regulationmentioning

confidence: 88%

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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: 88%

“…Interaction partners of TCTP in this context are the small GTPase Rheb, an upstream regulator of mTOR (mechanistic target of rapamycin), and 14-3-3 proteins (Le et al 2016). Knockout of TCTP in plants (Arabidopsis thaliana) resulted in a male gametophytic phenotype with impaired pollen tube growth.…”

Section: Roles For Tctp In Early Developmentmentioning

confidence: 99%

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

Bommer

2017

Results and Problems in Cell Differentiation

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“…Fortilin TCTP also contributes to the pathogenesis of diabetic nephropathy [150] and is important for the adaptive expansion of pancreatic β-cells in response to obesity and increased insulin requirement [36] and the regeneration of liver after hepatectomy [31]. Fortilin TCTP does this most likely by positively regulating the mTOR signaling pathway [34, 35, 57–59]. The protection by fortilin TCTP of the liver against acute alcohol injury is mediated by its ability to interact with and potentiate the activity of PRX1[12].…”

Section: Discussionmentioning

confidence: 99%

“…These data suggested that fortilin TCTP promotes cell growth and proliferation during development by binding to Rheb and positively regulating its activity [34]. The same group also reported that Drosophila 14-3-3 proteins are required to promote the interaction between fortilin TCTP and Rheb, and the loss of 14-3-3-proteins critically impaired organ growth during Drosophila development [35]. It is likely that the developmental role of fortilin TCTP is both the prevention of inappropriate apoptosis and the facilitation of cell proliferation and growth through the negative and positive regulations of the apoptosis [2, 20, 21] and mTOR growth pathways [34, 35], respectively (Fig.…”

Section: Fortilintctp In Human Diseases and Developmental Abnormalmentioning

confidence: 99%

“…GEFs stimulate the release of GDP from the protein to allow it to bind GTP and then facilitate the conversion of inactive Rheb:GDP to active Rheb:GTP [57]. Although the physical interaction between fortilin TCTP and Rheb has been questioned by two independent groups [60, 61], Le and coworkers showed that intact 14-3-3 proteins are required for fortilin TCTP to bind Rheb [35], suggesting that the status of 14-3-3 proteins could have potentially contributed to the failure to reproduce fortilin TCTP –Rheb interaction data [60, 61]. Despite the controversy about the mechanism of action [60, 61], phenotypic and genetic studies using Drosophila and Arabidopsis thaliana support the premise that fortilin TCTP increases cell size, cell number, and organ size, most likely through activation of the mTOR cell growth and proliferation pathway [34, 35, 62, 63].…”

Section: Introductionmentioning

confidence: 99%

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Fortilin: A Potential Target for the Prevention and Treatment of Human Diseases

Pinkaew

Fujise

2017

Advances in Clinical Chemistry

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Fortilin is a highly conserved 172-amino-acid polypeptide found in the cytosol, nucleus, mitochondria, extracellular space, and circulating blood. It is a multifunctional protein that protects cells against apoptosis, promotes cell growth and cell cycle progression, binds calcium (Ca2+), and has anti-pathogen activities. Its role in the pathogenesis of human and animal diseases is also diverse. Fortilin facilitates the development of atherosclerosis, contributes to both systemic and pulmonary arterial hypertension, participates in the development of cancers, and worsens diabetic nephropathy. It is important for the adaptive expansion of pancreatic β-cells in response to obesity and increased insulin requirement, for the regeneration of liver after hepatectomy, and for protection of the liver against alcohol- and ER stress-induced injury. Fortilin is a viable surrogate marker for in vivo apoptosis, and it plays a key role in embryo and organ development in vertebrates. In fish and shrimp, fortilin participates in host defense against bacterial and viral pathogens. Further translational research could prove fortilin to be a viable molecular target for treatment of various human diseases including and not limited to atherosclerosis, hypertension, certain tumors, diabetes mellitus, diabetic nephropathy, hepatic injury, and aberrant immunity and host defense.

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Structural Insights into TCTP and Its Interactions with Ligands and Proteins

Assrir

Malard

Lescop

2017

Results and Problems in Cell Differentiation

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The 19-24 kDa Translationally Controlled Tumor Protein (TCTP) is involved in a wide range of molecular interactions with biological and nonbiological partners of various chemical compositions such as proteins, peptides, nucleic acids, carbohydrates, or small molecules. TCTP is therefore an important and versatile binding platform. Many of these protein-protein interactions have been validated, albeit only few received an in-depth structural characterization. In this chapter, we will focus on the structural analysis of TCTP and we will review the available literature regarding its interaction network from a structural perspective.

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14-3-3 proteins regulate Tctp–Rheb interaction for organ growth in Drosophila

Cited by 42 publications

References 52 publications

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

Fortilin: A Potential Target for the Prevention and Treatment of Human Diseases

Structural Insights into TCTP and Its Interactions with Ligands and Proteins

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