Calcium lights up cell cycle

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-κB links the ion flux to a well-known cell cycle control gene, cyclin D1.

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-κB activation, which is required for cell cycle entry and transcription of cyclin D1, a rate-limiting G1 cyclin.

To determine whether the brief Ca²⁺ flux was crucial for NF-κB 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-κB activity. However, the scavenger was only effective when activated immediately after serum stimulation.

The Ca²⁺ flux is necessary but not sufficient to induce NF-κB activity. The researchers find that p42/p44 MAPK activity, which is dependent on both Ca²⁺ and probably other signals, is also required for NF-κB activation and cyclin D1 transcription. ▪