Recognition and cleavage of related to ubiquitin 1 (Rub1) and Rub1-ubiquitin chains by components of the ubiquitin-proteasome system

Singh, Rajesh K.; Zerath, Sylvia; Kleifeld, Oded; Scheffner, Martin; Glickman, Michael H.; Fushman, David

Recognition and cleavage of related to ubiquitin 1 (Rub1) and Rub1-ubiquitin chains by components of the ubiquitin-proteasome system

Dateien

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Datum

2012

Autor:innen

Singh, Rajesh K.

Zerath, Sylvia

Kleifeld, Oded

Scheffner, Martin

Glickman, Michael H.

Fushman, David

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Molecular & Cellular Proteomics. 2012, 11(12), pp. 1595-1611. ISSN 1535-9476. eISSN 1535-9484. Available under: doi: 10.1074/mcp.M112.022467

Zusammenfassung

Of all ubiquitin-like proteins, Rub1 (Nedd8 in mammals) is the closest kin of ubiquitin. We show via NMR that structurally, Rub1 and ubiquitin are fundamentally similar as well. Despite these profound similarities, the prevalence of Rub1/Nedd8 and of ubiquitin as modifiers of the proteome is starkly different, and their attachments to specific substrates perform different functions. Recently, some proteins, including p53, p73, EGFR, caspase-7, and Parkin, have been shown to be modified by both Rub1/Nedd8 and ubiquitin within cells. To understand whether and how it might be possible to distinguish among the same target protein modified by Rub1 or ubiquitin or both, we examined whether ubiquitin receptors can differentiate between Rub1 and ubiquitin. Surprisingly, Rub1 interacts with proteasome ubiquitin-shuttle proteins comparably to ubiquitin but binds more weakly to a proteasomal ubiquitin receptor Rpn10. We identified Rub1-ubiquitin heteromers in yeast and Nedd8-Ub heteromers in human cells. We validate that in human cells and in vitro, human Rub1 (Nedd8) forms chains with ubiquitin where it acts as a chain terminator. Interestingly, enzymatically assembled K48-linked Rub1-ubiquitin heterodimers are recognized by various proteasomal ubiquitin shuttles and receptors comparably to K48-linked ubiquitin homodimers. Furthermore, these heterologous chains are cleaved by COP9 signalosome or 26S proteasome. A derubylation function of the proteasome expands the repertoire of its enzymatic activities. In contrast, Rub1 conjugates may be somewhat resilient to the actions of other canonical deubiquitinating enzymes. Taken together, these findings suggest that once Rub1/Nedd8 is channeled into ubiquitin pathways, it is recognized essentially like ubiquitin.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

SINGH, Rajesh K., Sylvia ZERATH, Oded KLEIFELD, Martin SCHEFFNER, Michael H. GLICKMAN, David FUSHMAN, 2012. Recognition and cleavage of related to ubiquitin 1 (Rub1) and Rub1-ubiquitin chains by components of the ubiquitin-proteasome system. In: Molecular & Cellular Proteomics. 2012, 11(12), pp. 1595-1611. ISSN 1535-9476. eISSN 1535-9484. Available under: doi: 10.1074/mcp.M112.022467

BibTex

@article{Singh2012-12Recog-21935,
  year={2012},
  doi={10.1074/mcp.M112.022467},
  title={Recognition and cleavage of related to ubiquitin 1 (Rub1) and Rub1-ubiquitin chains by components of the ubiquitin-proteasome system},
  number={12},
  volume={11},
  issn={1535-9476},
  journal={Molecular & Cellular Proteomics},
  pages={1595--1611},
  author={Singh, Rajesh K. and Zerath, Sylvia and Kleifeld, Oded and Scheffner, Martin and Glickman, Michael H. and Fushman, David}
}

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