Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

J. Cell Biol. 191 (5): 967-979

Copyright © 2010 by the Rockefeller University Press.


Article

ERK1/2 MAP kinases promote cell cycle entry by rapid, kinase-independent disruption of retinoblastoma–lamin A complexes

Javier Rodríguez1, Fernando Calvo1, José M. González2, Berta Casar1, Vicente Andrés2, , and Piero Crespo1

1 Instituto de Biomedicina y Biotecnología de Cantabria, Consejo Superior de Investigaciones Científicas, Investigación Desarrollo e Innovación Cantabria, Departamento de Biología Molecular, Facultad de Medicina, Universidad de Cantabria, 39011 Santander, Spain
2 Laboratoria de Patofisiología Cardiovascular Molecular y Genética, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain

Correspondence to Piero Crespo: crespop{at}unican.es

Abstract: As orchestrators of essential cellular processes like proliferation, ERK1/2 mitogen-activated protein kinase signals impact on cell cycle regulation. A-type lamins are major constituents of the nuclear matrix that also control the cell cycle machinery by largely unknown mechanisms. In this paper, we disclose a functional liaison between ERK1/2 and lamin A whereby cell cycle progression is regulated. We demonstrate that lamin A serves as a mutually exclusive dock for ERK1/2 and the retinoblastoma (Rb) protein. Our results reveal that, immediately after their postactivation entrance in the nucleus, ERK1/2 dislodge Rb from its interaction with lamin A, thereby facilitating its rapid phosphorylation and consequently promoting E2F activation and cell cycle entry. Interestingly, these effects are independent of ERK1/2 kinase activity. We also show that cellular transformation and tumor cell proliferation are dependent on the balance between lamin A and nuclear ERK1/2 levels, which determines Rb accessibility for phosphorylation/inactivation.


Abbreviations: DK, kinase-deficient mutant • DMEM, Dulbecco’s minimum essential medium • ERK, ERK1/2 MAPK • ERNF, extraction-resistant nuclear fraction • FRET, fluorescence resonance energy transfer • GDI, guanine dissociation inhibitor • MEF, mouse embryo fibroblast • Rb, retinoblastoma • SNF, soluble nuclear fraction • wt, wild type



THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Arabidopsis thaliana mitogen-activated protein kinase 6 is involved in seed formation and modulation of primary and lateral root development.
J. S. Lopez-Bucio, J. G. Dubrovsky, J. Raya-Gonzalez, Y. Ugartechea-Chirino, J. Lopez-Bucio, L. A. de Luna-Valdez, M. Ramos-Vega, P. Leon, and A. A. Guevara-Garcia (2014)
J. Exp. Bot. 65, 169-183
   Abstract »    Full Text »    PDF »
The Nuclear Import of Oncoprotein Hepatitis B X-interacting Protein Depends on Interacting with c-Fos and Phosphorylation of Both Proteins in Breast Cancer Cells.
Y. Zhang, Y. Zhao, H. Li, Y. Li, X. Cai, Y. Shen, H. Shi, L. Li, Q. Liu, X. Zhang, et al. (2013)
J. Biol. Chem. 288, 18961-18974
   Abstract »    Full Text »    PDF »
Lamins at a glance.
C. Y. Ho and J. Lammerding (2012)
J. Cell Sci. 125, 2087-2093
   Full Text »    PDF »
The role of nuclear lamin B1 in cell proliferation and senescence.
T. Shimi, V. Butin-Israeli, S. A. Adam, R. B. Hamanaka, A. E. Goldman, C. A. Lucas, D. K. Shumaker, S. T. Kosak, N. S. Chandel, and R. D. Goldman (2011)
Genes & Dev. 25, 2579-2593
   Abstract »    Full Text »    PDF »
Working Without Kinase Activity: Phosphotransfer-Independent Functions of Extracellular Signal-Regulated Kinases.
J. Rodriguez and P. Crespo (2011)
Science Signaling 4, re3
   Abstract »    Full Text »    PDF »
Rb gets ERK'd by the competition.
B. Short (2010)
J. Cell Biol. 191, 894
   Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882