title: Rpn10 monoubiquitination orchestrates the association of the ubiquilin-type DSK2 receptor with the proteasome.
abstract: Despite the progress made in understanding the roles of proteasome polyubiquitin receptors, such as the subunits Rpn10 (regulatory particle non-ATPase 10) and Rpn13, and the transient interactors Rad23 (radiation sensitivity abnormal 23) and Dsk2 (dual-specificity protein kinase 2), the mechanisms involved in their regulation are virtually unknown. Rpn10, which is found in the cell in proteasome-bound and -unbound pools, interacts with Dsk2, and this interaction has been proposed to regulate the amount of Dsk2 that gains access to the proteasome. Rpn10 monoubiquitination has emerged as a conserved mechanism with a strong effect on Rpn10 function. In the present study, we show that functional yeast proteasomes have the capacity to associate and dissociate with Rpn10 and that Rpn10 monoubiquitination decreases the Rpn10-proteasome and Rpn10-Dsk2 associations. Remarkably, this process facilitates the formation of Dsk2-proteasomes in vivo. Therefore, Rpn10 monoubiquitination acts as mechanism that serves to switch the proteasome from an 'Rpn10 high/Dsk2 low' state to an 'Rpn10 low/Dsk2 high' state. Interestingly, Rpn10-ubiquitin, with an inactivated ubiquitin-interacting motif (UIM), and Dsk2(I45S), with an inactive ubiquitin-like domain (UBL), show temperature-dependent phenotypes with multiple functional interactions.
authors.affiliation: Institut de Biologia Molecular de Barcelona, CSIC, Barcelona Science Park, Baldiri i Reixac 15-21, 08028 Barcelona, Spain.
authors.forename: Alice
authors.initials: A
authors.lastname: Zuin
authors.affiliation: Institut de Biologia Molecular de Barcelona, CSIC, Barcelona Science Park, Baldiri i Reixac 15-21, 08028 Barcelona, Spain Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
authors.forename: Anne
authors.initials: A
authors.lastname: Bichmann
authors.affiliation: Institut de Biologia Molecular de Barcelona, CSIC, Barcelona Science Park, Baldiri i Reixac 15-21, 08028 Barcelona, Spain Department of Cell Biology, Harvard Medical School, Longwood, Boston, MA 02115, U.S.A.
authors.forename: Marta
authors.initials: M
authors.lastname: Isasa
authors.affiliation: Institut de Biologia Molecular de Barcelona, CSIC, Barcelona Science Park, Baldiri i Reixac 15-21, 08028 Barcelona, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Puig-Sàrries
authors.affiliation: Institut de Biologia Molecular de Barcelona, CSIC, Barcelona Science Park, Baldiri i Reixac 15-21, 08028 Barcelona, Spain.
authors.forename: Luís Miguel
authors.initials: LM
authors.lastname: Díaz
authors.affiliation: Institut de Biologia Molecular de Barcelona, CSIC, Barcelona Science Park, Baldiri i Reixac 15-21, 08028 Barcelona, Spain bernat.crosas@ibmb.csic.es.
authors.forename: Bernat
authors.initials: B
authors.lastname: Crosas
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C100415:DSK2 protein, S cerevisiae; C122019:RPN10 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D014452:Ubiquitins; D046988:Proteasome Endopeptidase Complex
keywords: Dsk2 (dual-specificity protein kinase 2); Rpn10 (regulatory particle non-ATPase 10); monoubiquitination; proteasome; ubiquitin