Stress-induced phosphorylation of S. pombe Atf1 abrogates its interaction with F box protein Fbh1.
dc.contributor.author | Lawrence, Clare L | |
dc.contributor.author | Jones, Nic | |
dc.contributor.author | Wilkinson, Caroline R M | |
dc.date.accessioned | 2010-08-09T15:27:19Z | |
dc.date.available | 2010-08-09T15:27:19Z | |
dc.date.issued | 2009-12-01 | |
dc.identifier.citation | Stress-induced phosphorylation of S. pombe Atf1 abrogates its interaction with F box protein Fbh1. 2009, 19 (22):1907-11 Curr. Biol. | en |
dc.identifier.issn | 1879-0445 | |
dc.identifier.pmid | 19836238 | |
dc.identifier.doi | 10.1016/j.cub.2009.09.044 | |
dc.identifier.uri | http://hdl.handle.net/10541/109305 | |
dc.description.abstract | 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. | |
dc.language.iso | en | en |
dc.subject.mesh | Activating Transcription Factor 1 | |
dc.subject.mesh | DNA Helicases | |
dc.subject.mesh | Phosphoproteins | |
dc.subject.mesh | Phosphorylation | |
dc.subject.mesh | Protein Binding | |
dc.subject.mesh | Schizosaccharomyces | |
dc.subject.mesh | Schizosaccharomyces pombe Proteins | |
dc.subject.mesh | Stress, Physiological | |
dc.title | Stress-induced phosphorylation of S. pombe Atf1 abrogates its interaction with F box protein Fbh1. | en |
dc.type | Article | en |
dc.contributor.department | Paterson Institute for Cancer Research, University of Manchester, UK. | en |
dc.identifier.journal | Current Biology | en |
html.description.abstract | 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. |