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Cells
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Role of TCTP in Cell Biological and Disease Processes
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Role of TCTP in Cell Biological and Disease Processes

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (15 November 2019) | Viewed by 38608

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Ulrich-Axel Bommer

E-Mail Website
Guest Editor
School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia
Interests: translational regulation of gene expression; cell stress response; cancer cell biology; cellular growth regulation
Prof. Dr. Toshiaki Kawakami

E-Mail Website
Guest Editor
Division of Cell Biology, La Jolla Institute for Immunology, San Diego, CA 92093, USA
Interests: allergy; mast cell; signal transduction

Special Issue Information

Dear Colleagues,

Translationally controlled tumour protein TCTP is a highly conserved, multifunctional protein present in almost all eukaryotic organisms. The protein is distinct from any other known protein families, but it interacts with a wide variety of client proteins. TCTP’s biological function can be broadly described as being cytoprotective; it is involved in promoting cell growth and developmental processes, and it protects cells under a range of biological stress conditions. Apart from acting at the cellular level, TCTP has been shown to be involved in extracellular functions that are typically part of anti-parasitic defence mechanisms or other aspects of host–parasite interactions.

Given the involvement of TCTP in several core cell biological processes, it is not surprising that an increasing number of diseases are being identified, where dysregulation of TCTP is shown to be involved. Apart from being overexpressed in a large number of human cancers, TCTP is also dysregulated in metabolic diseases, in processes of the immune system and in diseases affecting the circulatory system. These findings did already lead to first explorations of the possibility to exploit TCTP as a potential drug target, in particular in the area of cancer and allergy research.

Despite the large number of publications and review articles already published on this peculiar protein, we expect ‘TCTP’ to have still more interesting surprises in store for us. We presume that this ‘Special Issue’ of Cells will provide a suitable platform to both report and/or summarize the latest developments in the field.

We look forward to your upcoming contributions.

Prof. Ulrich-Axel Bommer
Prof. Toshiaki Kawakami
Guest Editors

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Keywords

  • translationally controlled tumour protein TCTP (alternative designations: fortilin or histamine releasing factor HRF)
  • cell growth and developmental processes
  • cell stress reactions
  • apoptosis and autophagy
  • cancer and other disease processes

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Published Papers (9 papers)

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Editorial

Jump to: Research, Review

5 pages, 909 KiB  
Editorial
Role of TCTP in Cell Biological and Disease Processes
by Ulrich-Axel Bommer and Toshiaki Kawakami
Cells 2021, 10(9), 2290; https://doi.org/10.3390/cells10092290 - 2 Sep 2021
Cited by 10 | Viewed by 2398
Abstract
Translationally controlled tumor protein (TCTP), also referred to as histamine-releasing factor (HRF) or fortilin, is a multifunctional protein, expressed in essentially all eukaryotic organisms [...] Full article
(This article belongs to the Special Issue Role of TCTP in Cell Biological and Disease Processes)
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3 pages, 1108 KiB  
Editorial
Obituary for Susan M. MacDonald, M.D.
by Alkis Togias, Marshall Plaut, Jackie Langdon, Ulrich-Axel Bommer and Adam Telerman
Cells 2021, 10(1), 87; https://doi.org/10.3390/cells10010087 - 7 Jan 2021
Cited by 1 | Viewed by 1545
Abstract
<inline-graphic xmlns:xlink="http://www [...] Full article
(This article belongs to the Special Issue Role of TCTP in Cell Biological and Disease Processes)

Research

Jump to: Editorial, Review

26 pages, 4182 KiB  
Article
DHA Affects Microtubule Dynamics Through Reduction of Phospho-TCTP Levels and Enhances the Antiproliferative Effect of T-DM1 in Trastuzumab-Resistant HER2-Positive Breast Cancer Cell Lines
by Silvia D’Amico, Ewa Krystyna Krasnowska, Isabella Manni, Gabriele Toietta, Silvia Baldari, Giulia Piaggio, Marco Ranalli, Alessandra Gambacurta, Claudio Vernieri, Flavio Di Giacinto, Francesca Bernassola, Filippo de Braud and Maria Lucibello
Cells 2020, 9(5), 1260; https://doi.org/10.3390/cells9051260 - 19 May 2020
Cited by 14 | Viewed by 4930
Abstract
Trastuzumab emtansine (T-DM1) is an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugated to the microtubule-targeting agent emtansine (DM1). T-DM1 is an effective agent in the treatment of patients with HER2-positive breast cancer whose disease has progressed on the first-line trastuzumab containing [...] Read more.
Trastuzumab emtansine (T-DM1) is an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugated to the microtubule-targeting agent emtansine (DM1). T-DM1 is an effective agent in the treatment of patients with HER2-positive breast cancer whose disease has progressed on the first-line trastuzumab containing chemotherapy. However, both primary and acquired tumour resistance limit its efficacy. Increased levels of the phosphorylated form of Translationally Controlled Tumour Protein (phospho-TCTP) have been shown to be associated with a poor clinical response to trastuzumab therapy in HER2-positive breast cancer. Here we show that phospho-TCTP is essential for correct mitosis in human mammary epithelial cells. Reduction of phospho-TCTP levels by dihydroartemisinin (DHA) causes mitotic aberration and increases microtubule density in the trastuzumab-resistant breast cancer cells HCC1954 and HCC1569. Combinatorial studies show that T-DM1 when combined with DHA is more effective in killing breast cells compared to the effect induced by any single agent. In an orthotopic breast cancer xenograft model (HCC1954), the growth of the tumour cells resumes after having achieved a complete response to T-DM1 treatment. Conversely, DHA and T-DM1 treatment induces a severe and irreversible cytotoxic effect, even after treatment interruption, thus, improving the long-term efficacy of T-DM1. These results suggest that DHA increases the effect of T-DM1 as poison for microtubules and supports the clinical development of the combination of DHA and T-DM1 for the treatment of aggressive HER2-overexpressing breast cancer. Full article
(This article belongs to the Special Issue Role of TCTP in Cell Biological and Disease Processes)
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Graphical abstract

17 pages, 2669 KiB  
Article
Mmi1, the Yeast Ortholog of Mammalian Translationally Controlled Tumor Protein (TCTP), Negatively Affects Rapamycin-Induced Autophagy in Post-Diauxic Growth Phase
by Jana Vojtova and Jiri Hasek
Cells 2020, 9(1), 138; https://doi.org/10.3390/cells9010138 - 7 Jan 2020
Cited by 4 | Viewed by 3662
Abstract
Translationally controlled tumor protein (TCTP) is a multifunctional and highly conserved protein from yeast to humans. Recently, its role in non-selective autophagy has been reported with controversial results in mammalian and human cells. Herein we examine the effect of Mmi1, the yeast ortholog [...] Read more.
Translationally controlled tumor protein (TCTP) is a multifunctional and highly conserved protein from yeast to humans. Recently, its role in non-selective autophagy has been reported with controversial results in mammalian and human cells. Herein we examine the effect of Mmi1, the yeast ortholog of TCTP, on non-selective autophagy in budding yeast Saccharomyces cerevisiae, a well-established model system to monitor autophagy. We induced autophagy by nitrogen starvation or rapamycin addition and measured autophagy by using the Pho8Δ60 and GFP-Atg8 processing assays in WT, mmi1Δ, and in autophagy-deficient strains atg8Δ or atg1Δ. Our results demonstrate that Mmi1 does not affect basal or nitrogen starvation-induced autophagy. However, an increased rapamycin-induced autophagy is detected in mmi1Δ strain when the cells enter the post-diauxic growth phase, and this phenotype can be rescued by inserted wild-type MMI1 gene. Further, the mmi1Δ cells exhibit significantly lower amounts of reactive oxygen species (ROS) in the post-diauxic growth phase compared to WT cells. In summary, our study suggests that Mmi1 negatively affects rapamycin-induced autophagy in the post-diauxic growth phase and supports the role of Mmi1/TCTP as a negative autophagy regulator in eukaryotic cells. Full article
(This article belongs to the Special Issue Role of TCTP in Cell Biological and Disease Processes)
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24 pages, 6579 KiB  
Article
TCTP is Essential for Cell Proliferation and Survival during CNS Development
by Sung-Ho Chen, Chin-Hung Lu and Ming-Jen Tsai
Cells 2020, 9(1), 133; https://doi.org/10.3390/cells9010133 - 6 Jan 2020
Cited by 13 | Viewed by 3954
Abstract
Translationally controlled tumor-associated protein (TCTP) has been implicated in cell growth, proliferation, and apoptosis through interacting proteins. Although TCTP is expressed abundantly in the mouse brain, little is known regarding its role in the neurogenesis of the nervous system. We used Nestin-cre-driven [...] Read more.
Translationally controlled tumor-associated protein (TCTP) has been implicated in cell growth, proliferation, and apoptosis through interacting proteins. Although TCTP is expressed abundantly in the mouse brain, little is known regarding its role in the neurogenesis of the nervous system. We used Nestin-cre-driven gene-mutated mice to investigate the function of TCTP in the nervous system. The mice carrying disrupted TCTP in neuronal and glial progenitor cells died at the perinatal stage. The NestinCre/+; TCTPf/f pups displayed reduced body size at postnatal day 0.5 (P0.5) and a lack of milk in the stomach compared with littermate controls. In addition to decreased cell proliferation, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and caspase assay revealed that apoptosis was increased in newly committed TCTP-disrupted cells as they migrated away from the ventricular zone. The mechanism may be that the phenotype from specific deletion of TCTP in neural progenitor cells is correlated with the decreased expression of cyclins D2, E2, Mcl-1, Bcl-xL, hax-1, and Octamer-binding transcription factor 4 (Oct4) in conditional knockout mice. Our results demonstrate that TCTP is a critical protein for cell survival during early neuronal and glial differentiation. Thus, enhanced neuronal loss and functional defect in Tuj1 and doublecortin-positive neurons mediated through increased apoptosis and decreased proliferation during central nervous system (CNS) development may contribute to the perinatal death of TCTP mutant mice. Full article
(This article belongs to the Special Issue Role of TCTP in Cell Biological and Disease Processes)
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0 pages, 4368 KiB  
Article
TCTP from Loxosceles Intermedia (Brown Spider) Venom Contributes to the Allergic and Inflammatory Response of Cutaneous Loxoscelism
by Marianna Boia-Ferreira, Kamila G. Moreno, Alana B. C. Basílio, Lucas P. da Silva, Larissa Vuitika, Bruna Soley, Ana Carolina M. Wille, Lucélia Donatti, Katia C. Barbaro, Olga M. Chaim, Luiza Helena Gremski, Silvio S. Veiga and Andrea Senff-Ribeiro
Cells 2019, 8(12), 1489; https://doi.org/10.3390/cells8121489 - 22 Nov 2019
Cited by 14 | Viewed by 3851 | Correction
Abstract
LiTCTP is a toxin from the Translationally Controlled Tumor Protein (TCTP) family identified in Loxosceles brown spider venoms. These proteins are known as histamine-releasing factors (HRF). TCTPs participate in allergic and anaphylactic reactions, which suggest their potential role as therapeutic targets. The histaminergic [...] Read more.
LiTCTP is a toxin from the Translationally Controlled Tumor Protein (TCTP) family identified in Loxosceles brown spider venoms. These proteins are known as histamine-releasing factors (HRF). TCTPs participate in allergic and anaphylactic reactions, which suggest their potential role as therapeutic targets. The histaminergic effect of TCTP is related to its pro-inflammatory functions. An initial characterization of LiTCTP in animal models showed that this toxin can increase the microvascular permeability of skin vessels and induce paw edema in a dose-dependent manner. We evaluated the role of LiTCTP in vitro and in vivo in the inflammatory and allergic aspects that undergo the biological responses observed in Loxoscelism, the clinical condition after an accident with Loxosceles spiders. Our results showed LiTCTP recombinant toxin (LiRecTCTP) as an essential synergistic factor for the dermonecrotic toxin actions (LiRecDT1, known as the main toxin in the pathophysiology of Loxoscelism), revealing its contribution to the exacerbated inflammatory response clinically observed in envenomated patients. Full article
(This article belongs to the Special Issue Role of TCTP in Cell Biological and Disease Processes)
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Review

Jump to: Editorial, Research

20 pages, 362 KiB  
Review
Dysregulation of TCTP in Biological Processes and Diseases
by Ulrich-Axel Bommer and Adam Telerman
Cells 2020, 9(7), 1632; https://doi.org/10.3390/cells9071632 - 7 Jul 2020
Cited by 39 | Viewed by 6884
Abstract
Translationally controlled tumor protein (TCTP), also called histamine releasing factor (HRF) or fortilin, is a multifunctional protein present in almost all eukaryotic organisms. TCTP is involved in a range of basic cell biological processes, such as promotion of growth and development, or cellular [...] Read more.
Translationally controlled tumor protein (TCTP), also called histamine releasing factor (HRF) or fortilin, is a multifunctional protein present in almost all eukaryotic organisms. TCTP is involved in a range of basic cell biological processes, such as promotion of growth and development, or cellular defense in response to biological stresses. Cellular TCTP levels are highly regulated in response to a variety of physiological signals, and regulatory mechanism at various levels have been elucidated. Given the importance of TCTP in maintaining cellular homeostasis, it is not surprising that dysregulation of this protein is associated with a range of disease processes. Here, we review recent progress that has been made in the characterisation of the basic biological functions of TCTP, in the description of mechanisms involved in regulating its cellular levels and in the understanding of dysregulation of TCTP, as it occurs in disease processes such as cancer. Full article
(This article belongs to the Special Issue Role of TCTP in Cell Biological and Disease Processes)
12 pages, 669 KiB  
Review
Regulation of Autophagy Is a Novel Tumorigenesis-Related Activity of Multifunctional Translationally Controlled Tumor Protein
by Ji-Sun Lee, Eun-Hwa Jang, Hyun Ae Woo and Kyunglim Lee
Cells 2020, 9(1), 257; https://doi.org/10.3390/cells9010257 - 20 Jan 2020
Cited by 10 | Viewed by 4344
Abstract
Translationally controlled tumor protein (TCTP) is highly conserved in eukaryotic organisms and plays multiple roles regulating cellular growth and homeostasis. Because of its anti-apoptotic activity and its role in the regulation of cancer metastasis, TCTP has become a promising target for cancer therapy. [...] Read more.
Translationally controlled tumor protein (TCTP) is highly conserved in eukaryotic organisms and plays multiple roles regulating cellular growth and homeostasis. Because of its anti-apoptotic activity and its role in the regulation of cancer metastasis, TCTP has become a promising target for cancer therapy. Moreover, growing evidence points to its clinical role in cancer prognosis. How TCTP regulates cellular growth in cancer has been widely studied, but how it regulates cellular homeostasis has received relatively little attention. This review discusses how TCTP is related to cancer and its potential as a target in cancer therapeutics, including its novel role in the regulation of autophagy. Regulation of autophagy is essential for cell recycling and scavenging cellular materials to sustain cell survival under the metabolic stress that cancer cells undergo during their aggressive proliferation. Full article
(This article belongs to the Special Issue Role of TCTP in Cell Biological and Disease Processes)
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10 pages, 1332 KiB  
Review
Histamine-Releasing Factor, a New Therapeutic Target in Allergic Diseases
by Yu Kawakami, Kazumi Kasakura and Toshiaki Kawakami
Cells 2019, 8(12), 1515; https://doi.org/10.3390/cells8121515 - 26 Nov 2019
Cited by 20 | Viewed by 6064
Abstract
Histamine-releasing activities on human basophils have been studied as potential allergy-causing agents for four decades. An IgE-dependent histamine-releasing factor (HRF) was recently shown to interact with a subset of immunoglobulins. Peptides or recombinant proteins that block the interactions between HRF and IgE have [...] Read more.
Histamine-releasing activities on human basophils have been studied as potential allergy-causing agents for four decades. An IgE-dependent histamine-releasing factor (HRF) was recently shown to interact with a subset of immunoglobulins. Peptides or recombinant proteins that block the interactions between HRF and IgE have emerged as promising anti-allergic therapeutics, as administration of them prevented or ameliorated type 2 inflammation in animal models of allergic diseases such as asthma and food allergy. Basic and clinical studies support the notion that HRF amplifies IgE-mediated activation of mast cells and basophils. We discuss how secreted HRF promotes allergic inflammation in vitro and in vivo complex disease settings. Full article
(This article belongs to the Special Issue Role of TCTP in Cell Biological and Disease Processes)
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