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.


Logo for

J. Cell Biol. 177 (2): 253-264

Copyright © 2007 by the Rockefeller University Press.


Regulation of the G2–M cell cycle progression by the ERK5–NF{kappa}B signaling pathway

Kelly Cude1, Yupeng Wang2, Hyun-Jung Choi2, Shih-Ling Hsuan2, Honglai Zhang3, Cun-Yu Wang3, , and Zhengui Xia1,2

1 Graduate Program in Molecular and Cellular Biology and 2 Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195
3 Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109

Correspondence to Zhengui Xia: zxia{at}

Abstract: Elucidation of mechanisms regulating cell cycle progression is of fundamental importance for cell and cancer biology. Although several genes and signaling pathways are implicated in G1–S regulation, less is known regarding the mechanisms controlling cell cycle progression through G2 and M phases. We report that extracellular signal–regulated kinase 5 (ERK5), a member of the mitogen-activated protein kinases, is activated at G2–M and required for timely mitotic entry. Stimulation of ERK5 activated nuclear factor {kappa}B (NF{kappa}B) through ribosomal S6 kinase 2 (RSK2)-mediated phosphorylation and degradation of I{kappa}B. Furthermore, selective inhibition of NF{kappa}B at G2–M phases substantially delayed mitotic entry and inhibited transcription of G2–M–specific genes, including cyclin B1, cyclin B2, Plk-1, and cdc25B. Moreover, inhibition of NF{kappa}B at G2–M diminished mitosis induced by constitutive activation of ERK5, providing a direct link between ERK5, NF{kappa}B, and regulation of G2–M progression. We conclude that a novel ERK5–NF{kappa}B signaling pathway plays a key role in regulation of the G2–M progression.

K. Cude and Y. Wang contributed equally to this paper.

Abbreviations used in this paper: ca, constitutive-active; dn, dominant-negative; ERK, extracellular signal–regulated kinase; HFF, human foreskin fibroblast; hSMC, human artery smooth muscle cell; MBP, myelin basic protein; NF{kappa}B, nuclear factor {kappa}B; Plk, polo-like kinase; RSK, ribosomal S6 kinase; SR, super repressor; wt, wild-type.

Role of Extracellular Signal-regulated Kinase 5 in Adipocyte Signaling.
H. Zhu, S. Guariglia, W. Li, D. Brancho, Z. V. Wang, P. E. Scherer, and C.-W. Chow (2014)
J. Biol. Chem. 289, 6311-6322
   Abstract »    Full Text »    PDF »
Japonicone A Suppresses Growth of Burkitt Lymphoma Cells through Its Effect on NF-{kappa}B.
X. Li, X. Yang, Y. Liu, N. Gong, W. Yao, P. Chen, J. Qin, H. Jin, J. Li, R. Chu, et al. (2013)
Clin. Cancer Res. 19, 2917-2928
   Abstract »    Full Text »    PDF »
Targeted Deletion of ERK5 MAP Kinase in the Developing Nervous System Impairs Development of GABAergic Interneurons in the Main Olfactory Bulb and Behavioral Discrimination between Structurally Similar Odorants.
J. Zou, Y.-W. Pan, Z. Wang, S.-Y. Chang, W. Wang, X. Wang, C. Tournier, D. R. Storm, and Z. Xia (2012)
J. Neurosci. 32, 4118-4132
   Abstract »    Full Text »    PDF »
Targeting the BMK1 MAP Kinase Pathway in Cancer Therapy.
Q. Yang and J.-D. Lee (2011)
Clin. Cancer Res. 17, 3527-3532
   Abstract »    Full Text »    PDF »
Multiple Facets of NF-{kappa}B in the Heart: To Be or Not to NF-{kappa}B.
J. W. Gordon, J. A. Shaw, and L. A. Kirshenbaum (2011)
Circ. Res. 108, 1122-1132
   Abstract »    Full Text »    PDF »
NFX1 Plays a Role in Human Papillomavirus Type 16 E6 Activation of NF{kappa}B Activity.
M. Xu, R. A. Katzenellenbogen, C. Grandori, and D. A. Galloway (2010)
J. Virol. 84, 11461-11469
   Abstract »    Full Text »    PDF »
Multisite phosphorylation of Erk5 in mitosis.
E. DIaz-RodrIguez and A. Pandiella (2010)
J. Cell Sci. 123, 3146-3156
   Abstract »    Full Text »    PDF »
Macrophage Wnt7b is critical for kidney repair and regeneration.
S.-L. Lin, B. Li, S. Rao, E.-J. Yeo, T. E. Hudson, B. T. Nowlin, H. Pei, L. Chen, J. J. Zheng, T. J. Carroll, et al. (2010)
PNAS 107, 4194-4199
   Abstract »    Full Text »    PDF »
ERK5 Activity Is Required for Nerve Growth Factor-induced Neurite Outgrowth and Stabilization of Tyrosine Hydroxylase in PC12 Cells.
Y. Obara, A. Yamauchi, S. Takehara, W. Nemoto, M. Takahashi, P. J. S. Stork, and N. Nakahata (2009)
J. Biol. Chem. 284, 23564-23573
   Abstract »    Full Text »    PDF »
Myocardin inhibits cellular proliferation by inhibiting NF-{kappa}B(p65)-dependent cell cycle progression.
R.-h. Tang, X.-L. Zheng, T. E. Callis, W. E. Stansfield, J. He, A. S. Baldwin, D.-Z. Wang, and C. H. Selzman (2008)
PNAS 105, 3362-3367
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

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