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Glyceraldehyde 3-phosphate dehydrogenase is a SET-binding protein and regulates cyclin B-cdk1 activity

Abstract

We report here that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interacts in vitro and in vivo with the protein SET. This interaction is performed through the acidic domain of SET located at the carboxy terminal region. On analysing the functional relevance of SET-GAPDH interaction, we observed that GAPDH reverses in a dose-dependent manner, the inhibition of cyclin B-cdk1 activity produced by SET. Similarly to SET, GAPDH associates with cyclin B, suggesting that the regulation of cyclin B-cdk1 activity might be mediated not only by the interaction of GAPDH with SET but also with cyclin B. To analyse the putative role of GAPDH on cell cycle progression, HCT116 cells were transfected with a GAPDH expression vector. Results indicate that overexpression of GAPDH does not affect the timing of DNA replication but induces an increase in the number of mitosis, an advancement of the peak of cyclin B-cdk1 activity and an acceleration of cell cycle progression. All these results suggest that GAPDH might be involved in cell cycle regulation by modulating cyclin B-cdk1 activity.

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Acknowledgements

We are grateful to Dr Sonia Brun for technical support and to Dr Núria Canela and Jorge Vera for their collaboration. Mass spectrometry analysis were performed at the ‘Unitat de proteòmica dels Serveis cientific-tècnics de la Universitat de Barcelona, Facultat de Medicina’. This work was supported by Grants SAF2002-00452, SAF 2003-08329, GEN2003-20243-C08 from the Ministerio de Educación y Ciencia of Spain. Financial support was also obtained from the networks of cooperative research on Cancer (C03/10) from the Instituto Carlos III.

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Correspondence to O Bachs.

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Carujo, S., Estanyol, J., Ejarque, A. et al. Glyceraldehyde 3-phosphate dehydrogenase is a SET-binding protein and regulates cyclin B-cdk1 activity. Oncogene 25, 4033–4042 (2006). https://doi.org/10.1038/sj.onc.1209433

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