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Biochem J. 2015 Aug 1;469(3):455-67. doi: 10.1042/BJ20141571. Epub 2015 Jun 11.

An intrinsically disordered region of RPN10 plays a key role in restricting ubiquitin chain elongation in RPN10 monoubiquitination.

Author information

1
Institut de Biologia Molecular de Barcelona, CSIC, Barcelona Science Park, Baldiri i Reixac 10-12, 08028 Barcelona, Spain Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta, 390, 08017 Barcelona, Spain.
2
Institut de Biologia Molecular de Barcelona, CSIC, Barcelona Science Park, Baldiri i Reixac 10-12, 08028 Barcelona, Spain.
3
Biomolecular NMR laboratory, Organic Chemistry Department, University of Barcelona, Baldiri Reixac 10-12, 08028 Barcelona, Spain.
4
Institut de Biologia Molecular de Barcelona, CSIC, Barcelona Science Park, Baldiri i Reixac 10-12, 08028 Barcelona, Spain bernat.crosas@ibmb.csic.es.

Abstract

Despite being a common mechanism in eukaryotes, the process by which protein monoubiquitination is produced and regulated in vivo is not completely understood. We present here the analysis of the process of monoubiquitination of the proteasomal subunit Rpn10 (regulatory particle non-ATPase 10), involved in the recruitment of polyubiquitinated substrates. Rpn10 is monoubiquitinated in vivo by the Nedd4 (neural precursor cell expressed developmentally down-regulated 4) enzyme Rsp5 (reverses SPT-phenotype protein 5) and this modification impairs the interaction of Rpn10 with substrates, having a regulatory effect on proteasome function. Remarkably, a disordered region near the ubiquitin-interacting motif of Rpn10 plays a role in the restriction of the polyubiquitin extension activity of Rsp5. Mutations in this disordered region promote ubiquitin chain extension of Rpn10. Thus, our work sheds light on the molecular basis and the functional relevance of a type of monoubiquitination that is driven by the substrate. Moreover, we uncover a putative role for disordered regions in modulating ubiquitin-protein ligation.

KEYWORDS:

E3 ubiquitin ligase; Rpn10; Rsp5; fold-back model; intrinsically disordered protein; monoubiquitination; polyubiquitin chain; proteasome; ubiquitin

PMID:
26205498
DOI:
10.1042/BJ20141571
[Indexed for MEDLINE]

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