Reference: Aviram S, et al. (2008) Autophosphorylation-induced degradation of the Pho85 cyclin Pcl5 is essential for response to amino acid limitation. Mol Cell Biol 28(22):6858-69

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Abstract


Pho85 cyclins (Pcls), activators of the yeast cyclin-dependent kinase (CDK) Pho85, belong together with the p35 activator of mammalian CDK5 to a distinct structural cyclin class. Different Pcls target Pho85 to distinct substrates. Pcl5 targets Pho85 specifically to Gcn4, a yeast transcription factor involved in the response to amino acid starvation, eventually causing the degradation of Gcn4. Pcl5 is itself highly unstable, an instability that was postulated to be important for regulation of Gcn4 degradation. We used hybrids between different Pcls to circumscribe the substrate recognition function to the core cyclin box domain of Pcl5. Furthermore, the cyclin hybrids revealed that Pcl5 degradation is uniquely dependent on two distinct degradation signals: one N-terminal and one C-terminal to the cyclin box domain. Whereas the C-terminal degradation signal is independent of Pho85, the N-terminal degradation signal requires phosphorylation of a specific threonine residue by the Pho85 molecule bound to the cyclin. This latter mode of degradation depends on the SCF ubiquitin ligase. Degradation of Pcl5 after self-catalyzed phosphorylation ensures that activity of the Pho85/Pcl5 complex is self-limiting in vivo. We demonstrate the importance of this mechanism for the regulation of Gcn4 degradation and for cell growth under conditions of amino acid starvation.

Reference Type
Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't
Authors
Aviram S, Simon E, Gildor T, Glaser F, Kornitzer D
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Phenotype Annotations 1 entry for 1 gene


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GenePhenotypeExperiment TypeMutant InformationStrain BackgroundChemicalDetails
PCL5resistance to chemicals: decreased
classical geneticsreduction of function
Allele: pcl5-T32A

blocks Pcl5p phosphorylation and subsequent Pcl5p degradation

W30330 mM amitrole
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Regulation Annotations 1 entry for 2 genes


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RegulatorTargetDirectionRegulation OfHappens DuringMethodEvidence
PHO85PCL5protein activityhigh-throughputexperimental evidence
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Post-translational Modifications


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Site Modification Modifier Reference

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Genetic Interactions

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Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions 2 entries for 3 genes

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InteractorInteractorAssayAnnotationActionModification

The in vitro phosphorylation assay included Pcl5.

GCN4PHO85Biochemical Activitymanually curatedHit-Baitphosphorylated residue
PCL5PHO85Biochemical Activitymanually curatedHit-Baitphosphorylated residue
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