A tryptophan-based assay method to search regulatory compounds for transcriptionally controlled tumor protein.

Transcriptionally controlled tumor protein (TCTP) is a highly conserved protein performing a large number of cellular functions by binding with various partner proteins. The importance of its roles in many diseases requires an assay method to find regulatory compounds. However, the molecular characteristics of TCTP made it difficult to search for chemicals interacting with it. In this study, a tryptophan-based assay method was designed and Y151W mutant TCTP was constructed to search binding chemicals. Since there is no tryptophan in the native sequence of TCTP, the incorporation of tryptophan in the Y151W mutant was very effective to establish the method. A flavonoid library was employed to the assay with the method. With the native and Y151W mutant TCTPs, three flavonoids such as morin, myricetin and isobavachalcone have been found to interact with TCTP. Combined with native gel electrophoresis, the binding region of isobavachalcone was suggested to be the flexible loop of TCTP. This approach can be easily applicable to find binding compounds of proteins with similar molecular characteristics of TCTP.

Meclizine, a piperazine-derivative antihistamine, binds to dimerized translationally controlled tumor protein and attenuates allergic reactions in a mouse model.

Translationally controlled tumor protein (TCTP), a highly conserved protein present in most eukaryotes, is involved in numerous biological processes. Only the dimeric form of TCTP (dTCTP) formed during inflammatory conditions exhibits cytokine-like activity. Therefore, dTCTP is considered as a therapeutic target for allergic diseases. Because monomeric TCTP (mTCTP) and dTCTP share a high topological similarity, we hypothesized that small molecules interacting with mTCTP would also bind to dTCTP and interfere with dTCTP-based cellular processes. In this study, nine compounds listed in the literature as interacting with mTCTP were investigated for their ability to suppress the activity of extracellular dTCTP in bronchial epithelial cells. It was found that one of the nine, meclizine, a piperazine-derivative antihistamine, significantly reduced IL-8 release and suppressed the NF-κB pathway. The direct interaction of meclizine with dTCTP was confirmed by surface plasmon resonance (SPR). Also, we found that meclizine can attenuate ovalbumin (OVA)-induced airway inflammation in mice. Therefore, meclizine might be a potential anti-allergic drug as an inhibitor for dTCTP.

Overexpression of translationally controlled tumor protein ameliorates metabolic imbalance and increases energy expenditure in mice.

BACKGROUND/OBJECTIVES: Translationally controlled tumor protein (TCTP) exhibits numerous biological functions. It has been shown to be involved in the regulation of glucose. However, its specific role in metabolism has not yet been clearly elucidated. Here, we aimed to assess the effect of TCTP overexpression on metabolic tissues and systemic energy metabolism. SUBJECTS/METHODS: We investigated whether TCTP can ameliorate the metabolic imbalance that causes obesity using TCTP-overexpressing transgenic (TCTP TG) mice. The mice were subjected to biochemical, morphological, physiological and protein expression studies to define the role of TCTP in metabolic regulation in response to normal chow diet (NCD) compared to high-fat diet (HFD) conditions, and cold environment. RESULTS: We found that TCTP TG mice show improved metabolic homeostasis under both of NCD and HFD conditions with simultaneous enhancements in glucose tolerance and insulin sensitivity. In particular, we found coincident increases in energy expenditure with significant upregulation of uncoupling protein 1 (UCP1) in the brown adipose tissue (BAT). Moreover, TCTP overexpressing mice exhibit significantly enhanced adaptive thermogenesis of BAT in response to cold exposure. CONCLUSIONS: Overexpression of TCTP ameliorated systemic metabolic homeostasis by stimulating UCP1-mediated thermogenesis in the BAT. This suggests that TCTP may function as a modulator of energy expenditure. This study suggests TCTP may serve as a therapeutic target for obesity and obesity-associated metabolic disorders including type 2 diabetes.

Regulation of Autophagy Is a Novel Tumorigenesis-Related Activity of Multifunctional Translationally Controlled Tumor Protein.

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.