Ubiquitin Chains Are Remodeled at the Proteasome by Opposing Ubiquitin Ligase and Deubiquitinating Activities

Bernat Crosas, John Hanna, Donald S. Kirkpatrick, Dan Phoebe Zhang, Yoshiko Tone, Nathaniel A Hathaway, Christa Buecker, David S. Leggett, Marion Schmidt, Randall W. King, Steven P Gygi, Daniel Finley

Research output: Contribution to journalArticle

204 Citations (Scopus)

Abstract

The ubiquitin ligase Hul5 was recently identified as a component of the proteasome, a multisubunit protease that degrades ubiquitin-protein conjugates. We report here a proteasome-dependent conjugating activity of Hul5 that endows proteasomes with the capacity to extend ubiquitin chains. hul5 mutants show reduced degradation of multiple proteasome substrates in vivo, suggesting that the polyubiquitin signal that targets substrates to the proteasome can be productively amplified at the proteasome. However, the products of Hul5 conjugation are subject to disassembly by a proteasome-bound deubiquitinating enzyme, Ubp6. A hul5 null mutation suppresses a ubp6 null mutation, suggesting that a balance of chain-extending and chain-trimming activities is required for proper proteasome function. As the association of Hul5 with proteasomes was found to be strongly stabilized by Ubp6, these enzymes may be situated in proximity to one another. We propose that through dynamic remodeling of ubiquitin chains, proteasomes actively regulate substrate commitment to degradation.

Original languageEnglish (US)
Pages (from-to)1401-1413
Number of pages13
JournalCell
Volume127
Issue number7
DOIs
StatePublished - Dec 29 2006
Externally publishedYes

Fingerprint

Proteasome Endopeptidase Complex
Ligases
Ubiquitin
Substrates
Polyubiquitin
Degradation
Mutation
Trimming
Enzymes
Peptide Hydrolases
Association reactions

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Crosas, B., Hanna, J., Kirkpatrick, D. S., Zhang, D. P., Tone, Y., Hathaway, NA., ... Finley, D. (2006). Ubiquitin Chains Are Remodeled at the Proteasome by Opposing Ubiquitin Ligase and Deubiquitinating Activities. Cell, 127(7), 1401-1413. https://doi.org/10.1016/j.cell.2006.09.051

Ubiquitin Chains Are Remodeled at the Proteasome by Opposing Ubiquitin Ligase and Deubiquitinating Activities. / Crosas, Bernat; Hanna, John; Kirkpatrick, Donald S.; Zhang, Dan Phoebe; Tone, Yoshiko; Hathaway, Nathaniel A; Buecker, Christa; Leggett, David S.; Schmidt, Marion; King, Randall W.; Gygi, Steven P; Finley, Daniel.

In: Cell, Vol. 127, No. 7, 29.12.2006, p. 1401-1413.

Research output: Contribution to journalArticle

Crosas, B, Hanna, J, Kirkpatrick, DS, Zhang, DP, Tone, Y, Hathaway, NA, Buecker, C, Leggett, DS, Schmidt, M, King, RW, Gygi, SP & Finley, D 2006, 'Ubiquitin Chains Are Remodeled at the Proteasome by Opposing Ubiquitin Ligase and Deubiquitinating Activities', Cell, vol. 127, no. 7, pp. 1401-1413. https://doi.org/10.1016/j.cell.2006.09.051
Crosas B, Hanna J, Kirkpatrick DS, Zhang DP, Tone Y, Hathaway NA et al. Ubiquitin Chains Are Remodeled at the Proteasome by Opposing Ubiquitin Ligase and Deubiquitinating Activities. Cell. 2006 Dec 29;127(7):1401-1413. https://doi.org/10.1016/j.cell.2006.09.051
Crosas, Bernat ; Hanna, John ; Kirkpatrick, Donald S. ; Zhang, Dan Phoebe ; Tone, Yoshiko ; Hathaway, Nathaniel A ; Buecker, Christa ; Leggett, David S. ; Schmidt, Marion ; King, Randall W. ; Gygi, Steven P ; Finley, Daniel. / Ubiquitin Chains Are Remodeled at the Proteasome by Opposing Ubiquitin Ligase and Deubiquitinating Activities. In: Cell. 2006 ; Vol. 127, No. 7. pp. 1401-1413.
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