Translationally controlled tumor protein acts as a guanine nucleotide dissociation inhibitor on the translation elongation factor eEF1A.
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 reversion/suppression 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, eEF1Bbeta, as TCTP-interacting partners. In vitro and in vivo studies confirmed that TCTP bound specifically eEF1Bbeta 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 eEF1Bbeta. These data suggest that TCTP has guanine nucleotide dissociation inhibitor activity, and, moreover, implicate TCTP in the elongation step of protein synthesis.
Cans
Christophe
C
Molecular Engines Laboratories, 20 Rue Bouvier, 75011 Paris, France.
Passer
Brent J
BJ
Shalak
Vyacheslav
V
Nancy-Portebois
Vanessa
V
Crible
Virginie
V
Amzallag
Nathalie
N
Allanic
David
D
Tufino
Rowena
R
Argentini
Manuela
M
Moras
Dino
D
Fiucci
Giusy
G
Goud
Bruno
B
Mirande
Marc
M
Amson
Robert
R
Telerman
Adam
A
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D004355:Drug Stability; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D020648:Peptide Elongation Factor 1 / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000090324:Tumor Protein, Translationally-Controlled 1; D020798:Two-Hybrid System Techniques
D014408:Biomarkers, Tumor; D020730:Guanine Nucleotide Dissociation Inhibitors; D006150:Guanine Nucleotides; D020648:Peptide Elongation Factor 1; D011993:Recombinant Fusion Proteins; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; D006153:Guanosine Diphosphate