Abstract
The proteasome is the central regulatory protease of eukaryotic cells. Heteroheptameric alpha-subunit and beta-subunit rings stack to form the 20S proteasome, which associates with a 19S regulatory particle (RP). Here we show that two yeast proteins, Pba3 and Pba4, form a previously unidentified 20S proteasome-assembly chaperone. Pba3-Pba4 interacts genetically and physically with specific proteasomal alpha subunits, and loss of Pba3-Pba4 causes both a reduction and a remodeling of cellular proteasomes. Notably, mutant cells accumulate proteasomes in which a second copy of the alpha4 subunit replaces alpha3. 20S proteasome-assembly defects also are associated with altered RP assembly; this unexpected result suggests that the 20S proteasome can function as an RP-assembly factor in vivo. Our data demonstrate that Pba3-Pba4 orchestrates formation of a specific type of proteasome, the first example of a trans-acting factor that controls assembly of alternative proteasomal complexes.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Computational Biology
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Metals, Heavy / toxicity
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Models, Biological
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Molecular Chaperones / chemistry
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Molecular Chaperones / metabolism*
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Multienzyme Complexes / chemistry
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Multienzyme Complexes / metabolism
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Mutant Proteins / chemistry
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Mutant Proteins / metabolism
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Mutation / genetics
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Proteasome Endopeptidase Complex / chemistry
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Proteasome Endopeptidase Complex / metabolism*
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Protein Binding / drug effects
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Protein Structure, Secondary
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Protein Subunits / chemistry
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Protein Subunits / metabolism
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Saccharomyces cerevisiae / cytology
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / enzymology*
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Saccharomyces cerevisiae / growth & development
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Saccharomyces cerevisiae Proteins / chemistry
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Saccharomyces cerevisiae Proteins / metabolism*
Substances
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IRC25 protein, S cerevisiae
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Metals, Heavy
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Molecular Chaperones
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Multienzyme Complexes
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Mutant Proteins
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POC4 protein, S cerevisiae
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Protein Subunits
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Saccharomyces cerevisiae Proteins
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Proteasome Endopeptidase Complex