Abstract
Endoplasmic Reticulum (ER)-associated degradation (ERAD) discards abnormal proteins synthesized in the ER. Through coordinated actions of ERAD components, misfolded/anomalous proteins are recognized, ubiquitinated, extracted from the ER and ultimately delivered to the proteasome for degradation. It is not well understood how ubiquitination of ERAD substrates is regulated. Here, we present evidence that the deubiquitinating enzyme Ubiquitin-Specific Protease 25 (USP25) is involved in ERAD. Our data support a model where USP25 counteracts ubiquitination of ERAD substrates by the ubiquitin ligase HRD1, rescuing them from degradation by the proteasome.
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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Animals
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COS Cells
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Chlorocebus aethiops
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Endoplasmic Reticulum / enzymology*
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Endoplasmic Reticulum / genetics
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Endoplasmic Reticulum-Associated Degradation / physiology*
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HEK293 Cells
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Humans
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Proteasome Endopeptidase Complex / genetics
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Proteasome Endopeptidase Complex / metabolism
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Proteolysis*
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Ubiquitin Thiolesterase / genetics
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Ubiquitin Thiolesterase / metabolism*
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / metabolism
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Ubiquitinated Proteins / genetics
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Ubiquitinated Proteins / metabolism*
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Ubiquitination / physiology
Substances
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USP25 protein, human
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Ubiquitinated Proteins
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SYVN1 protein, human
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Ubiquitin-Protein Ligases
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Ubiquitin Thiolesterase
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Proteasome Endopeptidase Complex