Regulation of the G2-M cell cycle progression by the ERK5-NFκB signaling pathway

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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 κB (NFκB) through ribosomal Só kinase 2 (RSK2)-mediated phosphorylation and degradation of IκB. Furthermore, selective inhibition of NFκB 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 NFκB at G2-M diminished mitosis induced by constitutive activation of ERK5, providing a direct link between ERK5, NFκB, and regulation of G2-M progression. We conclude that a novel ERK5-NFκB signaling pathway plays a key role in regulation of the G2-M progression. © The Rockefeller University Press.

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Cude, K., Wang, Y., Choi, H. J., Hsuan, S. L., Zhang, H., Wang, C. Y., & Xia, Z. (2007). Regulation of the G2-M cell cycle progression by the ERK5-NFκB signaling pathway. Journal of Cell Biology, 177(2), 253–264. https://doi.org/10.1083/jcb.200609166

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