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How ERK5 prompts proliferation

Overactive ERK5 drives cell proliferation and transformation and is associated with highly aggressive forms of breast and prostate cancer. Now, Cude et al. (page 253) reveal that this MAP kinase pushes the cell cycle forward by promoting entry into M phase.

ERK5 is activated by various growth factors. Its known targets include cyclin D and NFB, both of which help cells enter S phase. It had been suggested, therefore, that growth factor–induced ERK5 might promote cell proliferation by kick-starting S phase. No one had yet looked, however, at how ERK5 activity normally changes during the cell cycle.

Cude et al. have now done just that. They found that ERK5 activity peaked at G2/M phase, not S phase. Suppressing this activation reduced the number of cells entering mitosis, while overactivating ERK5 drove more cells into mitosis. The ERK5-driven entry into M phase was dependent on the activity of the transcription factor NFB, which the team found up-regulated a number of mitosis-promoting genes.

It's unclear yet whether high levels of ERK5 activity are a direct cause of cancer. But if high ERK5 is enough to overcome G2/M phase DNA damage checkpoints, as the team now plans to investigate, then mutations might accumulate over subsequent cell divisions. Given that ERK5 might also promote S phase entry, and that high ERK5 activity suppresses apoptosis, it's plausible that mutations causing ERK5 overactivity might be enough to drive aggressive tumor development.

Ruth Williams

ruth.williams{at}rockefeller.edu

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Related Article

Regulation of the G2–M cell cycle progression by the ERK5–NFB signaling pathway

Kelly Cude, Yupeng Wang, Hyun-Jung Choi, Shih-Ling Hsuan, Honglai Zhang, Cun-Yu Wang, and Zhengui Xia
J. Cell Biol. 2007 177: 253-264. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 943K) Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Williams, R. Search for Related Content PubMed Articles by Williams, R. Related Collections Related Article Social Bookmarking                            What's this?