ATM is involved in cell-cycle control through the regulation of retinoblastoma protein phosphorylation†
Article first published online: 8 MAR 2010
Copyright © 2010 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 110, Issue 1, pages 210–218, 1 May 2010
How to Cite
Pizarro, J. G., Folch, J., de la Torre, A. V., Junyent, F., Verdaguer, E., Jordan, J., Pallas, M. and Camins, A. (2010), ATM is involved in cell-cycle control through the regulation of retinoblastoma protein phosphorylation. J. Cell. Biochem., 110: 210–218. doi: 10.1002/jcb.22528
Javier G. Pizarro and Jaume Folch contributed equally to this work.
- Issue published online: 16 APR 2010
- Article first published online: 8 MAR 2010
- Manuscript Accepted: 12 JAN 2010
- Manuscript Received: 7 SEP 2009
- Ministerio de Educacion y Ciencia. Grant Numbers: SAF2009-13093, SAF2008-05143-C03-1
- Fondo de InvestigacionSanitaria
- Instituto de Salud Carlos III. Grant Number: PI080400
- Generalitat de Catalunya. Grant Number: 2009/SGR00853
- Fundacio la Marato TV3. Grant Number: 063230
- cell cycle;
- retinoblastoma protein
Ataxia telangiectasia mutated protein (ATM) is a member of the phosphatidylinositol-3 kinase (PI3K) family, which has a role in the cellular response to DNA double-strand breaks (DSBs). In the present study, we evaluated the role of ATM in cell-cycle control in dopaminergic rat neuroblastoma B65 cells. For this purpose, ATM activity was either inhibited pharmacologically with the specific inhibitor KU-55933, or the ATM gene was partially silenced by transfection with small interfering RNA (siRNA). Our data indicate that although ATM inhibition did not affect the cell cycle, both treatments specifically decreased the levels of cyclin A and retinoblastoma protein (pRb), phosphorylated at Ser780. Furthermore, ATM inhibition decreased the active form of p53, which is phosphorylated at Ser15, and also decreased Bax and p21 expression. Using H2O2 as a positive control of DSBs, caused a rapid pRb phosphorylation, this was prevented by KU-55933 and siRNA treatment. Collectively, our data demonstrate how a new molecular network on ATM regulates the cell cycle through the control of pRb phosphorylation. These findings support a new target of ATM. J. Cell. Biochem. 110: 210–218, 2010. © 2010 Wiley-Liss, Inc.