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Poly(ADP-ribosyl)ation is implicated in the G0–G1 transition of resting cells

Oncogene volume 27, pages 6083–6092 (2008)Cite this article

Abstract

Poly(ADP-ribosyl)ation, catalysed by a family of poly(ADP-ribose) polymerases (PARPs), plays an important role in a large variety of physiological processes, including cell proliferation, but its role in cell cycle progression is not yet completely defined. As reported here, the examination of early times following serum stimulation of quiescent fibroblasts suggests that poly(ADP-ribosyl)ation is necessary for the transition from the G0 phase to the G1 phase. We show that PARP activity is involved in this step through the regulation of immediate-early response genes, such as c-Fos and c-Myc. This is supported by the finding that exogenous Myc expression substantially restores cell cycle reactivation in the absence of polymer synthesis. Furthermore, using RNA interference, we show that PARP-1 is the PARP family member playing the most prominent role in the upregulation of c-Fos and c-Myc during G0–G1 transition. We report that even in lectin-stimulated peripheral blood mononucleated cells, the inhibition of PARP activity interferes with the upregulation of immediate-early genes and delays the induction of proliferation, suggesting a general role for PARP-1 in linking growth factor signaling with cell cycle entry.

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Acknowledgements

We thank Dr M Crescenzi for human FB 1329 cells, Professor G Palmieri for purified PBMCs and Dr B Amati for the c-MycER-expressing cells and for helpful suggestions. We are grateful to Professor P Caiafa for useful discussions on the ‘PARP world’. This work was supported by Grant no. 4179 from Associazione Italiana per la Ricerca sul Cancro (AIRC). MC was supported by a fellowship from AIRC/FIRC.

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Author notes

  1. M Carbone and M N Rossi: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cellular Biotechnology and Haematology, Pasteur Institute-Fondazione Cenci Bolognetti, University of Rome ‘La Sapienza’, Rome, Italy

    M Carbone, M N Rossi, M Cavaldesi, A Notari, P Amati & R Maione

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  1. M Carbone
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  2. M N Rossi
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Correspondence to P Amati.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Carbone, M., Rossi, M., Cavaldesi, M. et al. Poly(ADP-ribosyl)ation is implicated in the G0–G1 transition of resting cells. Oncogene 27, 6083–6092 (2008). https://doi.org/10.1038/onc.2008.221

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