Quantitative Proteomic Analysis of Tumor Reversion in Multiple Myeloma Cells

Ge, Feng; Zhang, Liang; Tao, Sheng-Ce; Kitazato, Kaio; Zhang, Zhiping; Zhang, Xian-En; Bi, Lijun

doi:10.1021/pr100992e

Cited by 26 publications

(22 citation statements)

References 66 publications

(198 reference statements)

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“…Another group used a proteomics approach to identify proteins that are down-regulated in a reversion model of multiple myeloma. They identified STAT3 and TCTP, among other proteins, as being down-regulated in revertant cells (Ge et al 2011). The tumour reversion model was instrumental to demonstrate the importance of TCTP in cancer, but the important question remained: What are the mechanisms, through which this protein is able to promote cancer?…”

Section: Mechanistic Involvement In Cancer Progressionmentioning

confidence: 99%

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: Mechanistic Involvement In Cancer Progressionmentioning

confidence: 99%

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

Bommer

2017

Results and Problems in Cell Differentiation

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“…STAT3 gene silencing was achieved by transfecting U266 cells with pSiStrike/STAT3 or pSiStrike/control vectors as described earlier. 32 Plasmid transfection was performed using a Nucleofector X005 (Amaxa). The resulting STAT3 knockdown and control cell lines were designated as U266-KD and U266-NC, respectively.…”

Section: Luciferase Assaysmentioning

confidence: 99%

Identification of Novel miR-21 Target Proteins in Multiple Myeloma Cells by Quantitative Proteomics

et al. 2012

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Substantial evidence indicates that microRNA-21 (miR-21) is a key oncomiR in carcinogenesis and is significantly elevated in multiple myeloma (MM). In this study, we explored the role of miR-21 in human MM cells and searched for miR-21 targets. By knocking down the expression of endogenous miR-21 in U266 myeloma cells, we observed reduced growth, an arrested cell cycle, and increased apoptosis. To further understand its molecular mechanism in the pathogenesis of MM, we employed a SILAC (stable isotope labeling by amino acids in cell culture)-based quantitative proteomic strategy to systematically identify potential targets of miR-21. In total, we found that the expression of 178 proteins was up-regulated significantly by miR-21 inhibition, implying that they could be potential targets of miR-21. Among these, the protein inhibitor of activated STAT3 (PIAS3) was confirmed as a direct miR-21 target by Western blotting and reporter gene assays. We further demonstrated that miR-21 enhances the STAT3-dependent signal pathway by inhibiting the function of PIAS3 and that down-regulation of PIAS3 contributes to the oncogenic function of miR-21. This elucidation of the role of PIAS3 in the miR-21-STAT3 positive regulatory loop not only may shed light on the molecular basis of the biological effects of miR-21 observed in MM cells but also has direct implications for the development of novel anti-MM therapeutic strategies.

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“…[ 78] sion phenotype' of transformed NIH3T3 cells and (3.) that reduction of TCTP levels raised the number of spontaneous revertants dramatically [77].…”

Section: Bommer Unpublished Results) • Tctp In the Tumour Reversionmentioning

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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Quantitative Proteomic Analysis of Tumor Reversion in Multiple Myeloma Cells

Cited by 26 publications

References 66 publications

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

Identification of Novel miR-21 Target Proteins in Multiple Myeloma Cells by Quantitative Proteomics

Cellular Function and Regulation of the Translationally Controlled Tumour Protein TCTP

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