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Abstract

The translationally controlled tumor-associated proteins (TCTPs) are a highly conserved and abundantly expressed family of eukaryotic proteins that are implicated in both cell growth and the human acute allergic response but whose intracellular biochemical function has remained elusive. We report here the solution structure of the TCTP from Schizosaccharomyces pombe, which, on the basis of sequence homology, defines the fold of the entire family. We show that TCTPs form a structural superfamily with the Mss4/Dss4 family of proteins, which bind to the GDP/GTP free form of Rab proteins (members of the Ras superfamily) and have been termed guanine nucleotide-free chaperones (GFCs). Mss4 also acts as a relatively inefficient guanine nucleotide exchange factor (GEF). We further show that the Rab protein binding site on Mss4 coincides with the region of highest sequence conservation in the TCTP family. This is the first link to any other family of proteins that has been established for the TCTP family and suggests the presence of a GFC/GEF at extremely high abundance in eukaryotic cells.

TSAP6 Facilitates the Secretion of Translationally Controlled Tumor Protein/Histamine-releasing Factor via a Nonclassical Pathway

“…In accordance, polo-like kinase was shown to interact directly with and phosphorylate TCTP, further implicating TCTP in cell cycle-related activities (14). More recently, NMR analysis revealed that TCTP has a structural homology with the mammalian suppressor of Sec4 (MSS4/DSS4), a protein that functions as a guanine nucleotide-free chaperone (15). In line with these findings, we recently identified a guanine nucle-* The costs of publication of this article were defrayed in part by the payment of page charges.…”

Characterization of the pumpkin Translationally-Controlled Tumor ProteinCmTCTP

“…The predicted 3D structure of this protein is quite similar to that of the canonical member of this family, from Schizosaccharomyces pombe, and to that predicted for most members of this family. 4,24 In general, the predicted structure of CmTCTP displays domains for tubulin and calcium binding, as well as a TCTP2, but not TCTP1, signature, among others. Thus, CmTCTP biochemical activity may be similar to mammalian and insect (Drosophila) TCTP.…”

Re-evaluating the Roles of Proposed Modulators of Mammalian Target of Rapamycin Complex 1 (mTORC1) Signaling

“…Chinese hamster ovary (CHO) cells were grown as described previously (43) in Dulbecco's modified Eagle's medium/Nutrient Mixture Ham's F-12 (Sigma) supplemented with 9% (v/v) fetal bovine serum, 100 g/ml streptomycin sulfate, and 100 units/ml penicillin G at 34°C. The tsH1 line was derived by Thompson et al (34) and contains a temperature-sensitive leucyl-tRNA synthetase that is active at 34°C but defective at 39.5°C.…”