201. Stress-Induced Phosphorylation of S. pombe Atf1 Abrogates Its Interaction with F Box Protein Fbh1
- Author
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Nic Jones, Clare Louise Lawrence, and Caroline Wilkinson
- Subjects
Plasma protein binding ,F-box protein ,General Biochemistry, Genetics and Molecular Biology ,Stress, Physiological ,Schizosaccharomyces ,Phosphorylation ,Protein kinase A ,Transcription factor ,Activating Transcription Factor 1 ,biology ,ATF1 ,Agricultural and Biological Sciences(all) ,Biochemistry, Genetics and Molecular Biology(all) ,DNA Helicases ,biology.organism_classification ,Phosphoproteins ,Molecular biology ,Ubiquitin ligase ,Cell biology ,biology.protein ,Schizosaccharomyces pombe Proteins ,General Agricultural and Biological Sciences ,MOLBIO ,Protein Binding - Abstract
SummaryThe 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.
- Published
- 2009
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