Reference: Willis SD, et al. (2022) Cyclin C-Cdk8 Kinase Phosphorylation of Rim15 Prevents the Aberrant Activation of Stress Response Genes. Front Cell Dev Biol 10:867257

Reference Help

Abstract


Cells facing adverse environmental cues respond by inducing signal transduction pathways resulting in transcriptional reprograming. In the budding yeast Saccharomyces cerevisiae, nutrient deprivation stimulates stress response gene (SRG) transcription critical for entry into either quiescence or gametogenesis depending on the cell type. The induction of a subset of SRGs require nuclear translocation of the conserved serine-threonine kinase Rim15. However, Rim15 is also present in unstressed nuclei suggesting that additional activities are required to constrain its activity in the absence of stress. Here we show that Rim15 is directly phosphorylated by cyclin C-Cdk8, the conserved kinase module of the Mediator complex. Several results indicate that Cdk8-dependent phosphorylation prevents Rim15 activation in unstressed cells. First, Cdk8 does not control Rim15 subcellular localization and rim15∆ is epistatic to cdk8∆ with respect to SRG transcription and the execution of starvation programs required for viability. Next, Cdk8 phosphorylates a residue in the conserved PAS domain in vitro. This modification appears important as introducing a phosphomimetic at Cdk8 target residues reduces Rim15 activity. Moreover, the Rim15 phosphomimetic only compromises cell viability in stresses that induce cyclin C destruction as well as entrance into meiosis. Taken together, these findings suggest a model in which Cdk8 phosphorylation contributes to Rim15 repression whilst it cycles through the nucleus. Cyclin C destruction in response to stress inactivates Cdk8 which in turn stimulates Rim15 to maximize SRG transcription and cell survival.

Reference Type
Journal Article
Authors
Willis SD, Hanley SE, Doyle SJ, Beluch K, Strich R, Cooper KF
Primary Lit For
Additional Lit For
Review For

Gene Ontology Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene/Complex Qualifier Gene Ontology Term Aspect Annotation Extension Evidence Method Source Assigned On Reference

Phenotype Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Disease Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Disease Ontology Term Qualifier Evidence Method Source Assigned On Reference

Regulation Annotations


Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Regulator Target Direction Regulation Of Happens During Method Evidence

Post-translational Modifications


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Site Modification Modifier Reference

Interaction Annotations


Genetic Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

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

Physical Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Assay Annotation Action Modification Source Reference

Functional Complementation Annotations


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Species Gene ID Strain background Direction Details Source Reference