Biochemical characterisation of TCTP questions its function as a guanine nucleotide exchange factor for Rheb

Rehmann, H.; Brüning, M.; Berghaus, C.; Schwarten, M.; Köhler, K.; Stocker, H.; Stoll, R.; Zwartkruis, F.J.; Wittinghofer, A.

doi:10.1016/j.febslet.2008.07.057

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Volume 582, Issue 20 , Pages 3005-3010, 3 September 2008

Biochemical characterisation of TCTP questions its function as a guanine nucleotide exchange factor for Rheb

Edited by Berend Wieringa

H. Rehmann
- Department of Physiological Chemistry and Center for Biomedical Genetics, UMC Utrecht Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
M. Brüning
- Abteilung Strukturelle Biologie Max-Planck-Institut für molekulare Physiologie, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany
C. Berghaus
- Biomolecular NMR, Faculty of Chemistry and Biochemistry, Ruhr-University of Bochum, 44780 Bochum, Germany
M. Schwarten
- Biomolecular NMR, Faculty of Chemistry and Biochemistry, Ruhr-University of Bochum, 44780 Bochum, Germany
K. Köhler
- Institute for Molecular Systems Biology, ETH Zurich, Wolfgang-Pauli-Strasse 16, CH-8093 Zurich, Switzerland
H. Stocker
- Institute for Molecular Systems Biology, ETH Zurich, Wolfgang-Pauli-Strasse 16, CH-8093 Zurich, Switzerland
R. Stoll
- Biomolecular NMR, Faculty of Chemistry and Biochemistry, Ruhr-University of Bochum, 44780 Bochum, Germany
- Corresponding authors.
F.J. Zwartkruis
- Department of Physiological Chemistry and Center for Biomedical Genetics, UMC Utrecht Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
- Corresponding authors.
A. Wittinghofer
- Abteilung Strukturelle Biologie Max-Planck-Institut für molekulare Physiologie, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany
- Corresponding authors.

Received 2 April 2008; received in revised form 19 June 2008; accepted 23 July 2008. published online 07 August 2008.

Abstract

Translationally controlled tumour protein (TCTP) is involved in malignant transformation and regulation of apoptosis. It has been postulated to serve as a guanine nucleotide exchange factor for the small G-protein Rheb. Rheb functions in the PI3 kinase/mTOR pathway. The study presented here was initiated to characterise the interaction between TCTP and Rheb biochemically. Since (i) no exchange activity of TCTP towards Rheb could be detected in vitro, (ii) no interaction between TCTP and Rheb could be detected by NMR spectroscopy, and (iii) no effect of TCTP depletion in cells on the direct downstream targets of Rheb could be observed in vivo, this study shows that TCTP is unlikely to be a guanine nucleotide exchange factor for Rheb.