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dc.contributor.authorLawrence, Clare Len
dc.contributor.authorJones, Nicen
dc.contributor.authorWilkinson, Caroline R Men
dc.date.accessioned2010-08-09T15:27:19Z
dc.date.available2010-08-09T15:27:19Z
dc.date.issued2009-12-01
dc.identifier.citationStress-induced phosphorylation of S. pombe Atf1 abrogates its interaction with F box protein Fbh1. 2009, 19 (22):1907-11 Curr. Biol.en
dc.identifier.issn1879-0445
dc.identifier.pmid19836238
dc.identifier.doi10.1016/j.cub.2009.09.044
dc.identifier.urihttp://hdl.handle.net/10541/109305
dc.description.abstractThe 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.isoenen
dc.subject.meshActivating Transcription Factor 1
dc.subject.meshDNA Helicases
dc.subject.meshPhosphoproteins
dc.subject.meshPhosphorylation
dc.subject.meshProtein Binding
dc.subject.meshSchizosaccharomyces
dc.subject.meshSchizosaccharomyces pombe Proteins
dc.subject.meshStress, Physiological
dc.titleStress-induced phosphorylation of S. pombe Atf1 abrogates its interaction with F box protein Fbh1.en
dc.typeArticleen
dc.contributor.departmentPaterson Institute for Cancer Research, University of Manchester, UK.en
dc.identifier.journalCurrent Biologyen
html.description.abstractThe 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.


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