Abstract
The tumor suppressor protein p53 is ubiquitinated and neddylated by MDM2 and then degraded by 26S proteasome. However, p53 is stabilized by the HAUSP (Herpes-virus-associated ubiquitin-specific protease) deubiquitinating enzyme. In this study, we discovered that rat HAUSP (rHAUSP) is polyubiquitinated, polyneddylated, and dimerized using co-immunoprecipitation assays. This suggests that rHAUSP may function as a dimer or multimer and is also degraded through the proteasome-mediated degradation. Transfection of rHAUSP into RGC-Lac-Z cell line with the integrated p53 response element revealed that rHAUSP contributed to p53 stabilization, and a rHAUSP (C224S) mutant contributed to p53 destabilization in a dose-dependent manner.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Cell Line
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Dimerization
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Endopeptidases / chemistry*
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Endopeptidases / genetics
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Endopeptidases / metabolism*
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Mice
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Nuclear Proteins / metabolism
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Proteasome Endopeptidase Complex / metabolism
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Protein Conformation
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Protein Isoforms / genetics
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Protein Isoforms / metabolism*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-mdm2
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Rats
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Tissue Distribution
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
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Ubiquitin Thiolesterase
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Ubiquitin-Specific Peptidase 7
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Ubiquitins / metabolism*
Substances
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Nuclear Proteins
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Protein Isoforms
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Proto-Oncogene Proteins
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Tumor Suppressor Protein p53
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Ubiquitins
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Mdm2 protein, mouse
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Mdm2 protein, rat
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Proto-Oncogene Proteins c-mdm2
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Endopeptidases
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USP7 protein, human
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Ubiquitin Thiolesterase
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Ubiquitin-Specific Peptidase 7
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Usp7 protein, rat
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Proteasome Endopeptidase Complex