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Calcium biologists have long suggested that there was a fundamental role for the cation in the cell cycle, but the supporting data have been largely circumstantial. Now, Sée et al. (page 661) have direct evidence for a transient Ca2 trigger in the initiation of the cell cycle upon serum stimulation. They also find that the transcription factor NF-B links the ion flux to a well-known cell cycle control gene, cyclin D1.
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Using Ca2 -sensitive dyes, the authors saw that serum-starved fibroblasts responded to serum stimulation with a rise in intracellular Ca2 that lasted for only 30 s. Serum addition also triggered NF-B activation, which is required for cell cycle entry and transcription of cyclin D1, a rate-limiting G1 cyclin.
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To determine whether the brief Ca2 flux was crucial for NF-B activation, the investigators introduced a caged Ca2 scavenger into the cells. Photoactivation of the Ca2 scavenger prevented the Ca2 flux that would naturally occur in response to serum stimulation and blocked NF-B activity. However, the scavenger was only effective when activated immediately after serum stimulation.
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- w4 A+ d& x9 K; a. \% RThe Ca2 flux is necessary but not sufficient to induce NF-B activity. The researchers find that p42/p44 MAPK activity, which is dependent on both Ca2 and probably other signals, is also required for NF-B activation and cyclin D1 transcription.(Preventing a Ca2 transient blocks NF-B ) |
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