Relative structural and functional roles of multiple deubiquitylating proteins associated with mammalian 26S proteasome

Elena Koulich, Xiaohua Li, George N. DeMartino

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

We determined composition and relative roles of deubiquitylating proteins associated with the 26S proteasome in mammalian cells. Three deubiquitylating activities were associated with the 26S proteasome: two from constituent subunits, Rpn11/S13 and Uch37, and one from a reversibly associated protein, Usp14. RNA interference (RNAi) of Rpn11/S13 inhibited cell growth, decreased cellular proteasome activity via disrupted 26S proteasome assembly, and inhibited cellular protein degradation. In contrast, RNAi of Uch37 or Usp14 had no detectable effect on cell growth, proteasome structure or proteolytic capacity, but accelerated cellular protein degradation. RNAi of both Uch37 and Usp14 also had no effect on proteasome structure or proteolytic capacity, but inhibited cellular protein degradation. Thus, proper proteasomal processing of ubiquitylated substrates requires Rpn11 plus either Uch37 or Usp14. Although the latter proteins feature redundant deubiquitylation functions, they also appear to exert noncatalyic effects on proteasome activity that are similar to but independent of one another. These results reveal unexpected functional relationships among multiple deubiquitylating proteins and suggest a model for mammalian 26S proteasome function whereby their concerted action governs proteasome function by linking deubiquitylation to substrate hydrolysis.

Original languageEnglish (US)
Pages (from-to)1072-1082
Number of pages11
JournalMolecular Biology of the Cell
Volume19
Issue number3
DOIs
StatePublished - Mar 2008

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Proteasome Endopeptidase Complex
5-chloro-3-tert-butyl-2'-chloro-4'-nitrosalicylanilide
RNA Interference
Proteolysis
Proteins
Growth
Hydrolysis
ATP dependent 26S protease

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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Relative structural and functional roles of multiple deubiquitylating proteins associated with mammalian 26S proteasome. / Koulich, Elena; Li, Xiaohua; DeMartino, George N.

In: Molecular Biology of the Cell, Vol. 19, No. 3, 03.2008, p. 1072-1082.

Research output: Contribution to journalArticle

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