At the turn of the century it seemed that the golden era of signal transduction might be at an end. The protein kinase cascades that mediate the intracellular actions of mitogens and growth factors had been worked out, at least in outline, and no new mechanisms for transmitting the intracellular actions of extracellular signals had been identified for some years. It therefore came like a bolt from the blue when Zhijian Chen's two papers appeared, reporting that Lys63‑linked ubiquitin chains were operating like 'second messengers' to transmit the intracellular actions of the cytokine interleukin‑1. Similar to the way in which the other second messengers exert their effects, these ubiquitin chains interact with a regulatory subunit of an intracellular protein kinase (TAK1) to switch on its catalytic activity. Why did these two papers have such a wide impact?