Critical Roles of Translationally Controlled Tumor Protein in the Homeostasis and TCR-Mediated Proliferation of Peripheral T Cells

Abstract

Translationally controlled tumor protein (TCTP) is expressed throughout T cell development and prominently induced following T cell activation. However, its function(s) during these processes is unclear. Here, we demonstrated that conditional deletion of TCTP before the β selection checkpoint resulted into a partial block of thymocyte development at the double-negative (DN) 3 stage. Deletion of TCTP in the double-positive (DP) stage did not cause any significant phenotype in the thymus except a slight increase of mature CD8 single-positive (SP) thymocytes. In contrast to the very modest phenotype observed in the thymus, a significant reduction of mature T cells was observed in the peripheral lymphoid organs of these two conditional null TCTP mutant mice. Detailed analysis revealed that the latter phenotype (peripheral T cell lymphopenia) was largely due to a decreased viability of mature TCTP-deficient (TCTP−/−) T cells. Transgenic expression of the anti-apoptotic protein Bcl-2 rescued the partial block of early thymocyte development, but not peripheral T cell lymphopenia of T-lineage-specific TCTP−/− mice, suggesting that the signaling networks of TCTP in these two processes are not identical. Last, we demonstrated that TCTP−/− T cells manifested a significant defect in T cell Ag receptor (TCR)-mediated cell proliferation. Further analysis revealed that such defect was due to a marked delay in the initial cell-cycle entry of TCTP−/− T cells following TCR stimulation. Together, these results indicate that TCTP plays a very modest role in thymocyte development, but is critical for peripheral T cell maintenance and TCR-mediated cell proliferation.

Extracellular translationally controlled tumor protein promotes colorectal cancer invasion and metastasis through Cdc42/JNK/ MMP9 signaling

“…Traditionally, TCTP is released from a series of immune cells (basophils [15], eosinophils [16] and thymus [17]) and some types of cancer cells (prostate cancer [18]). To verify whether TCTP could be secreted from CRC cells, TCTP concentration was determined by ELISA in the culture supernatant of six CRC cell lines cultured under normal conditions (10%FBS and normoxia), in serum-free medium (1%FBS and normoxia), in hypoxic (10%FBS and 1%O 2 ) conditions and in serum-free medium plus hypoxia (1%FBS and 1%O 2 ).…”

Translationally controlled tumor protein (TCTP) plays a pivotal role in cardiomyocyte survival through a Bnip3-dependent mechanism

“…The percentage of TUNEL-positive cells in embryos at day 5.5 showed no difference between wild-type and TCTP-deficient mice 21 . TCTP deletion in T cells caused no reduction in thymocyte numbers 25 . In addition, an inverse relationship between TCTP expression and growth rate was found with an epithelial cell line 26 .…”

Cellular Function and Regulation of the Translationally Controlled Tumour Protein TCTP

“…In 2009 two papers showed the importance of TCTP in preventing apoptotic cell death for the maintenance and development of T-cells. Using conditional TCTP knockout mouse models, Wu and colleagues [49] demonstrated that TCTP is essential for the viability of mature peripheral T-cells. Xiong et al [50] reported that IL-2 promotes the survival of regulatory T-cells through stimulation of TCTP expression.…”