title: JmjN interacts with JmjC to ensure selective proteolysis of Gis1 by the proteasome.
abstract: A group of JmjC domain-containing proteins also harbour JmjN domains. Although the JmjC domain is known to possess histone demethylase activity, the function of the JmjN domain remains largely undetermined. Previously, we have demonstrated that the yeast Gis1 transcription factor, bearing both JmjN and JmjC domains at its N terminus, is subject to proteasome-mediated selective proteolysis to downregulate its transcription activation ability. Here, we reveal that the JmjN and JmjC domains interact with each other through two β-sheets, one in each domain. Removal of either or both β-strands or the entire JmjN domain leads to complete degradation of Gis1, mediated partially by the proteasome. Mutating the core residues essential for histone demethylase activity demonstrated for other JmjC-containing proteins or deleting both Jumonji domains enhances the transcription activity of Gis1, but has no impact on its selective proteolysis by the proteasome. Together, these data suggest that JmjN and JmjC interact physically to form a structural unit that ensures the stability and appropriate transcription activity of Gis1.
authors.affiliation: Cambridge Systems Biology Centre and Department of Biochemistry, University of Cambridge, Sanger Building, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Quan
authors.affiliation: Cambridge Systems Biology Centre and Department of Biochemistry, University of Cambridge, Sanger Building, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Oliver
authors.affiliation: Cambridge Systems Biology Centre and Department of Biochemistry, University of Cambridge, Sanger Building, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
authors.forename: Nianshu
authors.initials: N
authors.lastname: Zhang
mesh_terms: D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D004718:Saccharomycetales / Q000201:enzymology* / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D005656:Fungal Proteins; D014157:Transcription Factors; D056484:Jumonji Domain-Containing Histone Demethylases; D046988:Proteasome Endopeptidase Complex