RPN4 is a Ligand, Substrate, and Transcriptional Regulator of the 26S Proteasome: A Negative Feedback Circuit
The RPN4 (SON1, UFD5) protein of the yeast Saccharomyces cerevisiae is required for normal levels of intracellular proteolysis. RPN4 is a transcriptional activator of genes encoding proteasomal subunits. Here we show that RPN4 is required for normal levels of these subunits. Further, we demonstrate...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2001-03, Vol.98 (6), p.3056-3061 |
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| creator | Xie, Youming Varshavsky, Alexander |
| description | The RPN4 (SON1, UFD5) protein of the yeast Saccharomyces cerevisiae is required for normal levels of intracellular proteolysis. RPN4 is a transcriptional activator of genes encoding proteasomal subunits. Here we show that RPN4 is required for normal levels of these subunits. Further, we demonstrate that RPN4 is extremely short-lived (t1/2 ≈2 min), that it directly interacts with RPN2, a subunit of the 26S proteasome, and that rpn4Δ cells are perturbed in their cell cycle. The degradation signal of RPN4 was mapped to its N-terminal region, outside the transcription-activation domains of RPN4. The ability of RPN4 to augment the synthesis of proteasomal subunits while being metabolically unstable yields a negative feedback circuit in which the same protein up-regulates the proteasome production and is destroyed by the assembled active proteasome. |
| doi_str_mv | 10.1073/pnas.071022298 |
| format | Article |
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RPN4 is a transcriptional activator of genes encoding proteasomal subunits. Here we show that RPN4 is required for normal levels of these subunits. Further, we demonstrate that RPN4 is extremely short-lived (t1/2 ≈2 min), that it directly interacts with RPN2, a subunit of the 26S proteasome, and that rpn4Δ cells are perturbed in their cell cycle. The degradation signal of RPN4 was mapped to its N-terminal region, outside the transcription-activation domains of RPN4. 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Varshavsky, Alexander</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c582t-87e9d1925d5c42c103d6860d41d29a9a902a345dc2cf55910e85b9448752d9293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Antibodies</topic><topic>B lymphocytes</topic><topic>Binding Sites</topic><topic>Biochemistry</topic><topic>Biological Sciences</topic><topic>Cell cycle</topic><topic>Cell Division</topic><topic>Cell growth</topic><topic>Cultured cells</topic><topic>Cysteine Endopeptidases - genetics</topic><topic>Cysteine Endopeptidases - metabolism</topic><topic>DNA</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Enzymes</topic><topic>Fungal Proteins - genetics</topic><topic>Fungal Proteins - metabolism</topic><topic>G1 Phase</topic><topic>Gene Expression Regulation</topic><topic>Genes</topic><topic>Immunoblotting</topic><topic>Ligands</topic><topic>Multienzyme Complexes - genetics</topic><topic>Multienzyme Complexes - metabolism</topic><topic>Peptide Hydrolases - metabolism</topic><topic>Proteasome Endopeptidase Complex</topic><topic>proteasomes 26S</topic><topic>Proteins</topic><topic>Ribonucleoproteins</topic><topic>Ribosomal Proteins - genetics</topic><topic>Ribosomal Proteins - metabolism</topic><topic>RNA-Binding Proteins - genetics</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>RPN4 protein</topic><topic>Saccharomyces cerevisiae</topic><topic>Saccharomyces cerevisiae Proteins</topic><topic>Substrate Specificity</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Ubiquitin - metabolism</topic><topic>Yeast</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xie, Youming</creatorcontrib><creatorcontrib>Varshavsky, Alexander</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xie, Youming</au><au>Varshavsky, Alexander</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RPN4 is a Ligand, Substrate, and Transcriptional Regulator of the 26S Proteasome: A Negative Feedback Circuit</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2001-03-13</date><risdate>2001</risdate><volume>98</volume><issue>6</issue><spage>3056</spage><epage>3061</epage><pages>3056-3061</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>The RPN4 (SON1, UFD5) protein of the yeast Saccharomyces cerevisiae is required for normal levels of intracellular proteolysis. 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| source | MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry; JSTOR |
| subjects | Antibodies B lymphocytes Binding Sites Biochemistry Biological Sciences Cell cycle Cell Division Cell growth Cultured cells Cysteine Endopeptidases - genetics Cysteine Endopeptidases - metabolism DNA DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Enzymes Fungal Proteins - genetics Fungal Proteins - metabolism G1 Phase Gene Expression Regulation Genes Immunoblotting Ligands Multienzyme Complexes - genetics Multienzyme Complexes - metabolism Peptide Hydrolases - metabolism Proteasome Endopeptidase Complex proteasomes 26S Proteins Ribonucleoproteins Ribosomal Proteins - genetics Ribosomal Proteins - metabolism RNA-Binding Proteins - genetics RNA-Binding Proteins - metabolism RPN4 protein Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Substrate Specificity Transcription Factors - genetics Transcription Factors - metabolism Ubiquitin - metabolism Yeast |
| title | RPN4 is a Ligand, Substrate, and Transcriptional Regulator of the 26S Proteasome: A Negative Feedback Circuit |
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