title: Phosphorylation by casein kinase 2 facilitates Psh1 protein-assisted degradation of Cse4 protein.
abstract: Cse4 is the centromeric histone H3 variant in budding yeast. Psh1 is an E3 ubiquitin ligase that controls Cse4 levels through proteolysis. Here we report that Psh1 is phosphorylated by the Cka2 subunit of casein kinase 2 (CK2) to promote its E3 activity for Cse4. Deletion of CKA2 significantly stabilized Cse4. Consistent with phosphorylation promoting the activity of Psh1, Cse4 was stabilized in a Psh1 phosphodepleted mutant strain in which the major phosphorylation sites were changed to alanines. Phosphorylation of Psh1 did not control Psh1-Cse4 or Psh1-Ubc3(E2) interactions. Although Cse4 was highly stabilized in a cka2Δ strain, mislocalization of Cse4 was mild, suggesting that Cse4 misincorporation was prevented by the intact Psh1-Cse4 association. Supporting this idea, Psh1 was also stabilized in a cka2Δ strain. Collectively our data suggest that phosphorylation is crucial in Psh1-assisted control of Cse4 levels and that the Psh1-Cse4 association itself functions to prevent Cse4 misincorporation.
authors.affiliation: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110 and.
authors.forename: Geetha S
authors.initials: GS
authors.lastname: Hewawasam
authors.affiliation: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110 and.
authors.forename: Mark
authors.initials: M
authors.lastname: Mattingly
authors.affiliation: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110 and.
authors.forename: Swaminathan
authors.initials: S
authors.lastname: Venkatesh
authors.affiliation: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110 and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110 and.
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.affiliation: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110 and.
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Workman
authors.affiliation: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110 and Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas 66160 jeg@stowers.org.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Gerton
mesh_terms: D047390:Casein Kinase II / Q000378:metabolism*; D002384:Catalysis; D002503:Centromere / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017353:Gene Deletion; D018386:Kinetochores; D010445:Peptide Elongation Factors / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: C092746:CSE4 protein, S cerevisiae; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D010445:Peptide Elongation Factors; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; C554184:Psh1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D047390:Casein Kinase II; D046988:Proteasome Endopeptidase Complex
keywords: CK2; Centromere; Cse4/CENP-A; E3 Ubiquitin Ligase; Phosphorylation; Proteolysis; Psh1; Yeast