The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

Abstract

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 ...

The permissive role of TCTP in PM2.5/NNK-induced epithelial–mesenchymal transition in lung cells

“…Thus, high levels of TCTP and vimentin might act as tumor enhancer for NSCLCs in both smokers and non-smokers (Additional file 1: Table S1). The results were consistent with the report that high TCTP levels were typically associated with advanced tumors and poor patient outcomes of brain tumor, breast cancer, colorectal cancer, hepatocellular carcinoma, neuroblastomas, and ovarian cancer [28].…”

“…Although TCTP was required for carcinogensinduced EMT, how PM 2.5 and NNK up-regulated TCTP expression remained unclear. Transcriptional regulation of TCTP gene via transcription factor such as CREB, P53, and HIF-1α has been reported [28], however, DNA methylation, the most studied epigenetic regulatory mechanism on transcriptional level, was not yet examined for TCTP. In our experiments, lower level of DNA methylation in TCTP promoter region and the discrepancy between NCI-H23 and Bet1A cells indicated that methylation did not play a key role in TCTP expression in PM 2.5 and NNK induced EMT (Additional file 1: Figure S2).…”

“…It has been reported that TCTP expression was regulated at both transcription and translation levels in cells [28], we hypothesized that the expression of TCTP could be regulated by microRNAs or/and by promotor methylation when lung cells were exposed to PM 2.5 and NNK. Predictions of microRNA candidates were made based on the 3′ UTRs of the TCTP gene using two bioinformatics tools: the mirSVR predicted target site scoring method [29] and the online tools at MicroRNA.org (http://www.micro rna.org).…”

LncRNA TPT1‐AS1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT1 expression

“…Tumor protein translationally controlled 1 is a multifunctional protein implicated in a diverse array of biological processes related to cell growth and tumor development; in addition, elevated TPT1 expression is strongly associated with aggressive tumor biological behavior, metastatic potential and poor prognosis . The PI3K/AKT signaling pathway has been observed in various cancers and can frequently modulate EOC metastasis, angiogenesis and chemoresistance, and corresponding inhibitors targeting this pathway, such as BKM120, GSK2110183 and AZD5363, are currently being evaluated as effective treatment strategies for EOC . Because the PI3K/AKT signaling pathway has been reported as a downstream factor for the maintenance of tumor malignancy by TPT1, we preliminarily proved that the knockdown of TPT1 in TPT1‐AS1‐overexpressing EOC cells could significantly impede tumor cell proliferation and metastasis in vitro and decrease the phosphorylation of PI3K and AKT, which indicated that TPT1‐AS1 might promote EOC tumorigenesis and dissemination through the TPT1/PI3K/AKT signaling pathway.…”

Systemic signalling throughTCTP1controls lateral root formation in Arabidopsis

“…It is known as an essential mitotic factor and a promoter of cellular growth interacting with the protein synthesis machinery, and also as a cytoprotective and anti-apopoptic protein (reviewed by [33, 34]). Although best characterised in animals given their high relevance to malignancy and cancer progression, these core functions appear largely conserved in other eukaryotes, including plants, and make TCTPs essential proteins to embryogenesis and early development, organ patterning, regulation of organ size and cellular homeostasis [34]. In Arabidopsis, knock-out mutations of either AtTCP1 or its homologue, AtTCTP2 are lethal [35, 36], as is the case of TCTP loss of function in mice [37] or drosophila [31].…”