QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 17, Issue 12, 5227-5240, December 2006

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E06-04-0284v1 17/12/5227    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shinohara, M. Articles by Rieder, C. L. Search for Related Content PubMed PubMed Citation Articles by Shinohara, M. Articles by Rieder, C. L.

Extracellular Signal-regulated Kinase 1/2 Activity Is Not Required in Mammalian Cells during Late G₂ for Timely Entry into or Exit from Mitosis

Mio Shinohara^*,, Alexei V. Mikhailov^*,, Julio A. Aguirre-Ghiso^,, and Conly L. Rieder^*,,

*Division of Molecular Medicine, Wadsworth Center, New York State Department of Health, Albany, NY 12201; Department of Biomedical Sciences, School of Public Health, and Gen*NY*Sis Center for Excellence in Cancer Genomics, State University of New York, Albany, NY 12144; and Marine Biology Laboratory, Woods Hole, MA 02543

Submitted April 7, 2006; Revised September 22, 2006; Accepted September 29, 2006
Monitoring Editor: Orna Cohen-Fix

Extracellular signal-regulated kinase (ERK)1/2 activity is reported to be required in mammalian cells for timely entry into and exit from mitosis (i.e., the G₂-mitosis [G₂/M] and metaphase-anaphase [M/A] transitions). However, it is unclear whether this involvement reflects a direct requirement for ERK1/2 activity during these transitions or for activating gene transcription programs at earlier stages of the cell cycle. To examine these possibilities, we followed live cells in which ERK1/2 activity was inhibited through late G₂ and mitosis. We find that acute inhibition of ERK1/2 during late G₂ and through mitosis does not affect the timing of the G₂/M or M/A transitions in normal or transformed human cells, nor does it impede spindle assembly, inactivate the p38 stress-activated checkpoint during late G₂ or the spindle assembly checkpoint during mitosis. Using CENP-F as a marker for progress through G₂, we also show that sustained inhibition of ERK1/2 transiently delays the cell cycle in early/mid-G₂ via a p53-dependent mechanism. Together, our data reveal that ERK1/2 activity is required in early G₂ for a timely entry into mitosis but that it does not directly regulate cell cycle progression from late G₂ through mitosis in normal or transformed mammalian cells.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-04-0284) on October 11, 2006.

Address correspondence to: Conly L. Rieder (rieder{at}wadsworth.org)

Abbreviations used: ERK, extracellular signal-regulated kinase; G₂/M, G₂-mitosis transition; IMF, immunofluorescence; M/A, metaphase-anaphase; NEB, nuclear envelope breakdown; SAC, spindle assembly checkpoint.

This article has been cited by other articles:

				T. Boutros, E. Chevet, and P. Metrakos Mitogen-Activated Protein (MAP) Kinase/MAP Kinase Phosphatase Regulation: Roles in Cell Growth, Death, and Cancer Pharmacol. Rev., September 1, 2008; 60(3): 261 - 310. [Abstract] [Full Text] [PDF]

				S. Pervin, A. H. Tran, S. Zekavati, J. M. Fukuto, R. Singh, and G. Chaudhuri Increased Susceptibility of Breast Cancer Cells to Stress Mediated Inhibition of Protein Synthesis Cancer Res., June 15, 2008; 68(12): 4862 - 4874. [Abstract] [Full Text] [PDF]