Ubxd1 is a novel co-factor of the human p97 ATPase
The AAA ATPase complex known as p97 or VCP in mammals and Cdc48 in yeast is connected to a multitude of cellular pathways, including membrane fusion, protein folding, protein degradation and activation of membrane-bound transcription factors. The mechanism by which p97 participates in such a broad s...
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| Veröffentlicht in: | The international journal of biochemistry & cell biology 2008, Vol.40 (12), p.2927-2942 |
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| container_title | The international journal of biochemistry & cell biology |
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| creator | Madsen, Louise Andersen, Katrine M. Prag, Søren Moos, Torben Semple, Colin A. Seeger, Michael Hartmann-Petersen, Rasmus |
| description | The AAA ATPase complex known as p97 or VCP in mammals and Cdc48 in yeast is connected to a multitude of cellular pathways, including membrane fusion, protein folding, protein degradation and activation of membrane-bound transcription factors. The mechanism by which p97 participates in such a broad spectrum of cellular functions appears to be via recruiting certain specific co-factors. Here we isolate and characterize the human protein Ubxd1, a novel co-factor of p97. We show that Ubxd1 is a stable protein that localizes to the cytoplasm and nucleus and is highly enriched in centrosomes. In mice Ubxd1 is widely expressed, but especially abundant in brain.
Curiously, Ubxd1 does not associate with p97 via its UBX domain, but via its PUB domain which binds the extreme C-terminus of p97. Phosphorylation of the penultimate tyrosine residue in p97 completely abolishes Ubxd1 interaction. Ternary complexes of Ubxd1, p47, and p97 were detected in vitro. Inhibition of Ubxd1 expression by siRNA did not affect the degradation of bulk protein or a model substrate of the ERAD pathway, indicating that Ubxd1 directs p97 activity to specialized functions in vivo. |
| doi_str_mv | 10.1016/j.biocel.2008.06.008 |
| format | Article |
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Curiously, Ubxd1 does not associate with p97 via its UBX domain, but via its PUB domain which binds the extreme C-terminus of p97. Phosphorylation of the penultimate tyrosine residue in p97 completely abolishes Ubxd1 interaction. Ternary complexes of Ubxd1, p47, and p97 were detected in vitro. Inhibition of Ubxd1 expression by siRNA did not affect the degradation of bulk protein or a model substrate of the ERAD pathway, indicating that Ubxd1 directs p97 activity to specialized functions in vivo.</description><identifier>ISSN: 1357-2725</identifier><identifier>EISSN: 1878-5875</identifier><identifier>DOI: 10.1016/j.biocel.2008.06.008</identifier><identifier>PMID: 18656546</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>AAA ATPase ; Adenosine Triphosphatases - chemistry ; Adenosine Triphosphatases - genetics ; Adenosine Triphosphatases - metabolism ; Amino Acid Sequence ; Carrier Proteins ; Cell Nucleus - genetics ; Cell Nucleus - metabolism ; Centrosome - metabolism ; Cytoplasm - genetics ; Cytoplasm - metabolism ; Degradation ; HeLa Cells ; Humans ; Immunohistochemistry ; Molecular Sequence Data ; Nuclear Proteins - chemistry ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; p97 ; Proteasome ; Protein Binding - genetics ; Protein Structure, Tertiary ; Proteins - chemistry ; Proteins - genetics ; Proteins - metabolism ; RNA, Small Interfering - metabolism ; Sequence Homology, Amino Acid ; Transfection ; Ubiquitin ; Ubiquitin - chemistry ; Ubiquitin - genetics ; Ubiquitin - metabolism</subject><ispartof>The international journal of biochemistry & cell biology, 2008, Vol.40 (12), p.2927-2942</ispartof><rights>2008 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c360t-d6e9f41836abba958897c4133dd7ada1a1dc5478cfd52030d8a59196119710e63</citedby><cites>FETCH-LOGICAL-c360t-d6e9f41836abba958897c4133dd7ada1a1dc5478cfd52030d8a59196119710e63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1357272508002598$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,4010,27900,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18656546$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Madsen, Louise</creatorcontrib><creatorcontrib>Andersen, Katrine M.</creatorcontrib><creatorcontrib>Prag, Søren</creatorcontrib><creatorcontrib>Moos, Torben</creatorcontrib><creatorcontrib>Semple, Colin A.</creatorcontrib><creatorcontrib>Seeger, Michael</creatorcontrib><creatorcontrib>Hartmann-Petersen, Rasmus</creatorcontrib><title>Ubxd1 is a novel co-factor of the human p97 ATPase</title><title>The international journal of biochemistry & cell biology</title><addtitle>Int J Biochem Cell Biol</addtitle><description>The AAA ATPase complex known as p97 or VCP in mammals and Cdc48 in yeast is connected to a multitude of cellular pathways, including membrane fusion, protein folding, protein degradation and activation of membrane-bound transcription factors. The mechanism by which p97 participates in such a broad spectrum of cellular functions appears to be via recruiting certain specific co-factors. Here we isolate and characterize the human protein Ubxd1, a novel co-factor of p97. We show that Ubxd1 is a stable protein that localizes to the cytoplasm and nucleus and is highly enriched in centrosomes. In mice Ubxd1 is widely expressed, but especially abundant in brain.
Curiously, Ubxd1 does not associate with p97 via its UBX domain, but via its PUB domain which binds the extreme C-terminus of p97. Phosphorylation of the penultimate tyrosine residue in p97 completely abolishes Ubxd1 interaction. Ternary complexes of Ubxd1, p47, and p97 were detected in vitro. Inhibition of Ubxd1 expression by siRNA did not affect the degradation of bulk protein or a model substrate of the ERAD pathway, indicating that Ubxd1 directs p97 activity to specialized functions in vivo.</description><subject>AAA ATPase</subject><subject>Adenosine Triphosphatases - chemistry</subject><subject>Adenosine Triphosphatases - genetics</subject><subject>Adenosine Triphosphatases - metabolism</subject><subject>Amino Acid Sequence</subject><subject>Carrier Proteins</subject><subject>Cell Nucleus - genetics</subject><subject>Cell Nucleus - metabolism</subject><subject>Centrosome - metabolism</subject><subject>Cytoplasm - genetics</subject><subject>Cytoplasm - metabolism</subject><subject>Degradation</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Molecular Sequence Data</subject><subject>Nuclear Proteins - chemistry</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>p97</subject><subject>Proteasome</subject><subject>Protein Binding - genetics</subject><subject>Protein Structure, Tertiary</subject><subject>Proteins - chemistry</subject><subject>Proteins - genetics</subject><subject>Proteins - metabolism</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Sequence Homology, Amino Acid</subject><subject>Transfection</subject><subject>Ubiquitin</subject><subject>Ubiquitin - chemistry</subject><subject>Ubiquitin - genetics</subject><subject>Ubiquitin - metabolism</subject><issn>1357-2725</issn><issn>1878-5875</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM9LwzAcxYMoTqf_gUhO3lqTpvl1EcbwFwz0sJ1DmqQso21m0w79783owJun9z289768DwB3GOUYYfa4yysfjGvyAiGRI5YnOQNXWHCRUcHpeboJ5VnBCzoD1zHuEEKYFuQSzLBglNGSXYFiU31bDH2EGnbh4BpoQlZrM4QehhoOWwe3Y6s7uJccLtafOrobcFHrJrrbk87B5uV5vXzLVh-v78vFKjOEoSGzzMm6xIIwXVVaUiEkNyUmxFqurcYaW0NLLkxtaYEIskJTiSXDWHKMHCNz8DD17vvwNbo4qNbHNLjRnQtjVEzSEnEpk7GcjKYPMfauVvvet7r_URipIyu1UxMrdWSlEFNJUuz-1D9WrbN_oROcZHiaDC6tPHjXq2i864yzvndmUDb4_z_8AuT9eUc</recordid><startdate>2008</startdate><enddate>2008</enddate><creator>Madsen, Louise</creator><creator>Andersen, Katrine M.</creator><creator>Prag, Søren</creator><creator>Moos, Torben</creator><creator>Semple, Colin A.</creator><creator>Seeger, Michael</creator><creator>Hartmann-Petersen, Rasmus</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>2008</creationdate><title>Ubxd1 is a novel co-factor of the human p97 ATPase</title><author>Madsen, Louise ; Andersen, Katrine M. ; Prag, Søren ; Moos, Torben ; Semple, Colin A. ; Seeger, Michael ; Hartmann-Petersen, Rasmus</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c360t-d6e9f41836abba958897c4133dd7ada1a1dc5478cfd52030d8a59196119710e63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>AAA ATPase</topic><topic>Adenosine Triphosphatases - chemistry</topic><topic>Adenosine Triphosphatases - genetics</topic><topic>Adenosine Triphosphatases - metabolism</topic><topic>Amino Acid Sequence</topic><topic>Carrier Proteins</topic><topic>Cell Nucleus - genetics</topic><topic>Cell Nucleus - metabolism</topic><topic>Centrosome - metabolism</topic><topic>Cytoplasm - genetics</topic><topic>Cytoplasm - metabolism</topic><topic>Degradation</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Molecular Sequence Data</topic><topic>Nuclear Proteins - chemistry</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>p97</topic><topic>Proteasome</topic><topic>Protein Binding - genetics</topic><topic>Protein Structure, Tertiary</topic><topic>Proteins - chemistry</topic><topic>Proteins - genetics</topic><topic>Proteins - metabolism</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Sequence Homology, Amino Acid</topic><topic>Transfection</topic><topic>Ubiquitin</topic><topic>Ubiquitin - chemistry</topic><topic>Ubiquitin - genetics</topic><topic>Ubiquitin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Madsen, Louise</creatorcontrib><creatorcontrib>Andersen, Katrine M.</creatorcontrib><creatorcontrib>Prag, Søren</creatorcontrib><creatorcontrib>Moos, Torben</creatorcontrib><creatorcontrib>Semple, Colin A.</creatorcontrib><creatorcontrib>Seeger, Michael</creatorcontrib><creatorcontrib>Hartmann-Petersen, Rasmus</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The international journal of biochemistry & cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Madsen, Louise</au><au>Andersen, Katrine M.</au><au>Prag, Søren</au><au>Moos, Torben</au><au>Semple, Colin A.</au><au>Seeger, Michael</au><au>Hartmann-Petersen, Rasmus</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ubxd1 is a novel co-factor of the human p97 ATPase</atitle><jtitle>The international journal of biochemistry & cell biology</jtitle><addtitle>Int J Biochem Cell Biol</addtitle><date>2008</date><risdate>2008</risdate><volume>40</volume><issue>12</issue><spage>2927</spage><epage>2942</epage><pages>2927-2942</pages><issn>1357-2725</issn><eissn>1878-5875</eissn><abstract>The AAA ATPase complex known as p97 or VCP in mammals and Cdc48 in yeast is connected to a multitude of cellular pathways, including membrane fusion, protein folding, protein degradation and activation of membrane-bound transcription factors. The mechanism by which p97 participates in such a broad spectrum of cellular functions appears to be via recruiting certain specific co-factors. Here we isolate and characterize the human protein Ubxd1, a novel co-factor of p97. We show that Ubxd1 is a stable protein that localizes to the cytoplasm and nucleus and is highly enriched in centrosomes. In mice Ubxd1 is widely expressed, but especially abundant in brain.
Curiously, Ubxd1 does not associate with p97 via its UBX domain, but via its PUB domain which binds the extreme C-terminus of p97. Phosphorylation of the penultimate tyrosine residue in p97 completely abolishes Ubxd1 interaction. Ternary complexes of Ubxd1, p47, and p97 were detected in vitro. Inhibition of Ubxd1 expression by siRNA did not affect the degradation of bulk protein or a model substrate of the ERAD pathway, indicating that Ubxd1 directs p97 activity to specialized functions in vivo.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>18656546</pmid><doi>10.1016/j.biocel.2008.06.008</doi><tpages>16</tpages></addata></record> |
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| subjects | AAA ATPase Adenosine Triphosphatases - chemistry Adenosine Triphosphatases - genetics Adenosine Triphosphatases - metabolism Amino Acid Sequence Carrier Proteins Cell Nucleus - genetics Cell Nucleus - metabolism Centrosome - metabolism Cytoplasm - genetics Cytoplasm - metabolism Degradation HeLa Cells Humans Immunohistochemistry Molecular Sequence Data Nuclear Proteins - chemistry Nuclear Proteins - genetics Nuclear Proteins - metabolism p97 Proteasome Protein Binding - genetics Protein Structure, Tertiary Proteins - chemistry Proteins - genetics Proteins - metabolism RNA, Small Interfering - metabolism Sequence Homology, Amino Acid Transfection Ubiquitin Ubiquitin - chemistry Ubiquitin - genetics Ubiquitin - metabolism |
| title | Ubxd1 is a novel co-factor of the human p97 ATPase |
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