Translationally controlled tumor protein acts as a guanine nucleotide dissociation inhibitor on the translation elongation factor eEF1A

Abstract

Recently, we demonstrated that the expression levels of the translationally controlled tumor protein (TCTP) were strongly down-regulated at the mRNA and protein levels during tumor reversion͞suppression and by the activation of p53 and Siah-1. To better characterize the function of TCTP, a yeast two-hybrid hunt was performed. Subsequent analysis identified the translation elongation factor, eEF1A, and its guanine nucleotide exchange factor, eEF1B␤, as TCTP-interacting partners. In vitro and in vivo studies confirmed that TCTP bound specifically eEF1B␤ and eEF1A. Additionally, MS analysis also identified eEF1A as a TCTP interactor. Because eEF1A is a GTPase, we investigated the role of TCTP on the nucleotide exchange reaction of eEF1A. Our results show that TCTP preferentially stabilized the GDP form of eEF1A, and, furthermore, impaired the GDP exchange reaction promoted by eEF1B␤. These data suggest that TCTP has guanine nucleotide dissociation inhibitor activity, and, moreover, implicate TCTP in the elongation step of protein synthesis.

Roles of the translationally controlled tumour protein (TCTP) and the double-stranded RNA-dependent protein kinase, PKR, in cellular stress responses

“…This observation is consistent with the demonstration that TCTP overexpression in mice results in systemic hypertension (Kim et al, 2008b); (2) TCTP interacts with protein synthesis elongation factor eEF1A and negatively regulates the guanosine-nucleotide-exchange reaction on eEF1A (Cans et al, 2003); (3) a study using gene knockdown in Drosophila reported the activity of TCTP as a guanine-nucleotide-exchange factor for the small GTPase, Rheb, and indicated involvement of TCTP in the target of rapamycin (TOR) signalling pathway (Hsu et al, 2007); however, recent results from our own (Wang et al, 2008) and two other laboratories (Chen et al, 2007;Rehmann et al, 2008) are not compatible with this conclusion.…”

Proteomics Identification of Differentially Expressed Proteins Associated with Pollen Germination and Tube Growth Reveals Characteristics of Germinated Oryza sativa Pollen

“…eIF4G, another member of the complex, is a large modular protein that serves as a docking site of translation-related proteins (37). TCTP is the key inhibitor of translation elongation; it inhibits guanine nucleotide dissociation from protein elongation factor 1A (EF1A) (38). Up-regulation of eIF4A and eIF4G and down-regulation of TCTP, together with up-regulation of molecular chaperones and amino acid metabolism-associated proteins (Table I), suggest greatly increased translational efficiency in growing pollen tubes; this is consistent with the notion that active protein synthesis is required for fast pollen tube growth (9).…”

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

“…The observations that the mRNA of TCTP also bears a 5 0 -TOP (Yamashita et al 2008;Meyuhas 2000) and is regulated through the mTORC1 pathway (Bommer et al 2015) would suggest that TCTP also participates in the activities (or regulation) of the translational machinery. In fact, as early as 2003, the Telerman group identified translation elongation factor eEF1A and its guanine nucleotide exchange factor eEF1Bβ as TCTP-interacting partners (Cans et al 2003). TCTP stabilised the GDP form of eEF1A, and impaired the GDP exchange reaction promoted by eEF1Bβ, thereby acting as an inhibitor of the GEF function, in contrast to the activation of the GEF activity of TCTP for Rheb, mentioned above.…”