Translationally Controlled Tumor Protein, a Dual Functional Protein Involved in the Immune Response of the Silkworm, Bombyx mori

Abstract

Insect gut immunity is the first line of defense against oral infection. Although a few immune-related molecules in insect intestine has been identified by genomics or proteomics approach with comparison to well-studied tissues, such as hemolymph or fat body, our knowledge about the molecular mechanism underlying the gut immunity which would involve a variety of unidentified molecules is still limited. To uncover additional molecules that might take part in pathogen recognition, signal transduction or immune regulation in insect intestine, a T7 phage display cDNA library of the silkworm midgut is constructed. By use of different ligands for biopanning, Translationally Controlled Tumor Protein (TCTP) has been selected. BmTCTP is produced in intestinal epithelial cells and released into the gut lumen. The protein level of BmTCTP increases at the early time points during oral microbial infection and declines afterwards. In vitro binding assay confirms its activity as a multi-ligand binding molecule and it can further function as an opsonin that promotes the phagocytosis of microorganisms. Moreover, it can induce the production of anti-microbial peptide via a signaling pathway in which ERK is required and a dynamic tyrosine phosphorylation of certain cytoplasmic membrane protein. Taken together, our results characterize BmTCTP as a dual-functional protein involved in both the cellular and the humoral immune response of the silkworm, Bombyx mori.

CRISPR disruption of TCTP gene impaired normal development in the silkworm Bombyx mori

“…A previous report has revealed high BmTCTP expression in the silkworm larval midgut and lower expression in PM (Wang et al ., ). RNAi‐mediated knockdown of midgut BmTCTP suppressed the innate intestinal immunity through disruption of dynamic ERK phosphorylation after oral microbial infection.…”

“…High and constitutive TCTP transcription have been reported in the silkworm (Lee et al, 2004). In the midgut, BmTCTP is equally distributed inside the intestinal epithelial cells, but a small quantity has been observed in the peritrophic membrane (PM) (Wang et al, 2013a). RNA interference (RNAi) knockdown in the larval midgut results in suppression of intestinal innate immunity after oral microbial infection in intact animals, and the dynamics of extracellular regulated protein kinases (ERK) phosphorylation is disrupted in the midgut in transgenic silkworms (Hu et al, 2015).…”

Fortilin: A Potential Target for the Prevention and Treatment of Human Diseases

“…Further, fortilin TCTP is secreted by cells, circulates in the blood, and serves as a viable surrogate marker for in vivo apoptosis [4]. Finally, in fish [130], shrimp [43, 45, 47–49, 52, 53], and silkworms [154, 155], fortilin TCTP participates in host defense against bacterial and viral pathogens through its ability to (a) recognize, bind, and facilitate degradation of the invaders when secreted into the extracellular space and (b) protect immune cells against pathogen-induced cell death while within the cell. Further research could prove fortilin TCTP to be a viable molecular target for diagnosing and treating various human diseases, including and not limited to atherosclerosis, hypertension, cancer, DM, DN, hepatic injury, and aberrant immunity and host defense (Figure 1).…”

“…Bm-Fortilin TCTP -coated Sm was phagocytosed by silkworm hemocytes more rapidly than was bovine serum albumin (BSA)-coated Sm . The addition of Bm-fortilin TCTP to the culture medium caused the silkworm cell line BmNSWU1 to upregulate the expression of Cecrophin A1 and Attacin, which are anti-microbial peptides (AMPs) [154]. The same group of investigators generated transgenic silkworms that tissue-specifically overexpressed siRNA against Bm-fortilin TCTP RNA.…”

Targeted Efficacy of Dihydroartemisinin for Translationally Controlled Protein Expression in a Lung Cancer Model

“…It has been shown to play an important role not only in physiological events, such as cell proliferation, cell death and immune responses, but also in stress response and tumor reversion (Wang et al, 2013;Ma et al, 2010;Lee et al, 2008;Susini et al, 2008;Dong et al, 2009;Nagano-Ito et al, 2012;Miao et al, 2013). Many researches show that TCTP level in tumor is higher than that in the corresponding normal tissues, indicating its critical role in tumorigenesis (Amson et al, 2011;Amson et al, 2013).…”