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- Title
Regulation of the G2-M cell cycle progression by the ERK5-NF<sub>Κ</sub>B signaling pathway.
- Authors
Cude, Kelly; Wang, Yupeng; Choi, Hyun-Jung; Hsuan, Shih-Ling; Zhang, Honglai; Wang, Cun-Yu; Xia, Zhengui; Cude, K.; Wang, Y.
- 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 S6 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.
- Subjects
CELL cycle; CYTOLOGY; CANCER; PROTEIN kinases; PHOSPHORYLATION; GENES; MITOSIS
- Publication
Journal of Cell Biology, 2007, Vol 177, Issue 2, p253
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200609166