title: A transcriptional activator is part of an SCF ubiquitin ligase to control degradation of its cofactors.
abstract: Multisubunit protein complexes pose a challenge to the coordinated regulation of individual components. We show how the yeast transactivating factor Met4 functions as a component of the SCF(Met30) ubiquitin ligase to synchronize its own activity with cofactor assembly. Cells maintain Met4 in a dormant state by a regulatory ubiquitin chain assembled by SCF(Met30). Nutritional and heavy-metal stress block Met4 ubiquitylation resulting in Met4 activation, which induces a stress-response program including cell-cycle arrest. Met4 relies on assembly with various cofactors for promoter binding. We report here that the stability of these DNA-binding cofactors is regulated by SCF(Met30). Remarkably, the transcriptional activator Met4 functions as a substrate-specificity factor in the context of SCF(Met30/Met4) to coordinate cofactor degradation with its own activity status. Our results establish an additional layer for substrate recruitment by SCF ubiquitin ligases and provide conceptual insight into coordinated regulation of protein complexes.
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Irvine, 240D Med Sci I, Irvine, CA 92697-1700, USA.
authors.forename: Ikram
authors.initials: I
authors.lastname: Ouni
authors.forename: Karin
authors.initials: K
authors.lastname: Flick
authors.forename: Peter
authors.initials: P
authors.lastname: Kaiser
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D044783:F-Box Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D044783:F-Box Proteins; C470285:MET30 protein, S cerevisiae; C073675:MET4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D043743:Ubiquitin-Protein Ligase Complexes