The Atf1 transcription factor is critical for directing stress-induced gene expression in fission yeast [1]. Upon exposure to stress, Atf1 is hyperphosphorylated by the mitogen-activated protein kinase (MAPK) Sty1 [2, 3], which results in its stabilization [4]. The resulting increase in Atf1 is vital for a robust response to certain stresses [4]. Here we investigated the mechanism by which phosphorylation stabilizes Atf1. We show that Atf1 is a target for the ubiquitin-proteasome system and that its degradation is dependent upon an SCF E3 ligase containing the F box protein Fbh1. Turnover of Atf1 requires an intact F box, but not DNA helicase activity of Fbh1. Accordingly, disruption of Fbh1 F box function suppresses phenotypes associated with loss of Atf1 phosphorylation. Atf1 and Fbh1 interact under basal conditions, but this binding is lost upon stress. In contrast, a version of Atf1 lacking all intact MAPK sites still interacts with Fbh1 upon stress, indicating that the association between the F box protein and substrate is disrupted by stress-induced phosphorylation. Most F box protein-substrate interactions described to date are mediated positively by phosphorylation [5]. Thus, our findings represent a novel means of regulating the interaction between an F box protein and its substrate. Moreover, Atf1 is the first target described in any organism for the Fbh1 F box protein.