CHIP Is Associated with Parkin, a Gene Responsible for Familial Parkinson's Disease, and Enhances Its Ubiquitin Ligase Activity
Unfolded Pael receptor (Pael-R) is a substrate of the E3 ubiquitin ligase Parkin. Accumulation of Pael-R in the endoplasmic reticulum (ER) of dopaminergic neurons induces ER stress leading to neurodegeneration. Here, we show that CHIP, Hsp70, Parkin, and Pael-R formed a complex in vitro and in vivo....
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| Veröffentlicht in: | Molecular cell 2002-07, Vol.10 (1), p.55-67 |
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| creator | Imai, Yuzuru Soda, Mariko Hatakeyama, Shigetsugu Akagi, Takumi Hashikawa, Tsutomu Nakayama, Kei-Ichi Takahashi, Ryosuke |
| description | Unfolded Pael receptor (Pael-R) is a substrate of the E3 ubiquitin ligase Parkin. Accumulation of Pael-R in the endoplasmic reticulum (ER) of dopaminergic neurons induces ER stress leading to neurodegeneration. Here, we show that CHIP, Hsp70, Parkin, and Pael-R formed a complex in vitro and in vivo. The amount of CHIP in the complex was increased during ER stress. CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. Moreover, CHIP enhanced Parkin-mediated in vitro ubiquitination of Pael-R in the absence of Hsp70. Furthermore, CHIP enhanced the ability of Parkin to inhibit cell death induced by Pael-R. Taken together, these results indicate that CHIP is a mammalian E4-like molecule that positively regulates Parkin E3 activity. |
| doi_str_mv | 10.1016/S1097-2765(02)00583-X |
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Accumulation of Pael-R in the endoplasmic reticulum (ER) of dopaminergic neurons induces ER stress leading to neurodegeneration. Here, we show that CHIP, Hsp70, Parkin, and Pael-R formed a complex in vitro and in vivo. The amount of CHIP in the complex was increased during ER stress. CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. Moreover, CHIP enhanced Parkin-mediated in vitro ubiquitination of Pael-R in the absence of Hsp70. Furthermore, CHIP enhanced the ability of Parkin to inhibit cell death induced by Pael-R. Taken together, these results indicate that CHIP is a mammalian E4-like molecule that positively regulates Parkin E3 activity.</description><identifier>ISSN: 1097-2765</identifier><identifier>EISSN: 1097-4164</identifier><identifier>DOI: 10.1016/S1097-2765(02)00583-X</identifier><identifier>PMID: 12150907</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Blotting, Western ; Cell Death ; Endoplasmic Reticulum - metabolism ; Gene Expression Regulation ; HSP70 Heat-Shock Proteins - metabolism ; Humans ; Ligases - genetics ; Ligases - metabolism ; Macromolecular Substances ; Male ; Mice ; Models, Biological ; Parkinsonian Disorders - enzymology ; Parkinsonian Disorders - genetics ; Parkinsonian Disorders - pathology ; Protein Binding ; Protein Folding ; Protein Transport ; Rats ; Rats, Wistar ; Substantia Nigra - ultrastructure ; Transfection ; Tumor Cells, Cultured ; Ubiquitin-Protein Ligases</subject><ispartof>Molecular cell, 2002-07, Vol.10 (1), p.55-67</ispartof><rights>2002 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-4e08c22ec623a659b4d73adc669a0e50081bfdf5c80c73185a9715a73dd2ee283</citedby><cites>FETCH-LOGICAL-c491t-4e08c22ec623a659b4d73adc669a0e50081bfdf5c80c73185a9715a73dd2ee283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S1097-2765(02)00583-X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12150907$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Imai, Yuzuru</creatorcontrib><creatorcontrib>Soda, Mariko</creatorcontrib><creatorcontrib>Hatakeyama, Shigetsugu</creatorcontrib><creatorcontrib>Akagi, Takumi</creatorcontrib><creatorcontrib>Hashikawa, Tsutomu</creatorcontrib><creatorcontrib>Nakayama, Kei-Ichi</creatorcontrib><creatorcontrib>Takahashi, Ryosuke</creatorcontrib><title>CHIP Is Associated with Parkin, a Gene Responsible for Familial Parkinson's Disease, and Enhances Its Ubiquitin Ligase Activity</title><title>Molecular cell</title><addtitle>Mol Cell</addtitle><description>Unfolded Pael receptor (Pael-R) is a substrate of the E3 ubiquitin ligase Parkin. Accumulation of Pael-R in the endoplasmic reticulum (ER) of dopaminergic neurons induces ER stress leading to neurodegeneration. Here, we show that CHIP, Hsp70, Parkin, and Pael-R formed a complex in vitro and in vivo. The amount of CHIP in the complex was increased during ER stress. CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. Moreover, CHIP enhanced Parkin-mediated in vitro ubiquitination of Pael-R in the absence of Hsp70. Furthermore, CHIP enhanced the ability of Parkin to inhibit cell death induced by Pael-R. Taken together, these results indicate that CHIP is a mammalian E4-like molecule that positively regulates Parkin E3 activity.</description><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cell Death</subject><subject>Endoplasmic Reticulum - metabolism</subject><subject>Gene Expression Regulation</subject><subject>HSP70 Heat-Shock Proteins - metabolism</subject><subject>Humans</subject><subject>Ligases - genetics</subject><subject>Ligases - metabolism</subject><subject>Macromolecular Substances</subject><subject>Male</subject><subject>Mice</subject><subject>Models, Biological</subject><subject>Parkinsonian Disorders - enzymology</subject><subject>Parkinsonian Disorders - genetics</subject><subject>Parkinsonian Disorders - pathology</subject><subject>Protein Binding</subject><subject>Protein Folding</subject><subject>Protein Transport</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Substantia Nigra - ultrastructure</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><subject>Ubiquitin-Protein Ligases</subject><issn>1097-2765</issn><issn>1097-4164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9v1DAQxSMEoqXwEUA-0VYiMHbiODlVq6V_VlqJCqjUm-XYEzqQTbYZb1FPfPVmdyNx7GlGo9-bJ72XJO8lfJYgiy8_JFQmVabQJ6BOAXSZpbcvksPdOZdF_nLat8hB8ob5N4DMdVm9Tg6kkhoqMIfJv_nV4losWMyYe08uYhB_Kd6Jazf8oe6TcOISOxTfkdd9x1S3KJp-EBduRS25duK4745ZfCVGxziKuiDOuzvXeWSxiCxuarrfUKROLOnXiIiZj_RA8fFt8qpxLeO7aR4lNxfnP-dX6fLb5WI-W6Y-r2RMc4TSK4W-UJkrdFXnwWQu-KKoHKAGKGXdhEb7ErzJZKldZaR2JgtBIaoyO0o-7v-uh_5-gxztithj27oO-w1bIysDBqpnQVnmBUi1BfUe9EPPPGBj1wOt3PBoJdhtRXZXkd3mb0HZXUX2dtR9mAw29QrDf9XUyQic7QEc83ggHCx7wjHKQAP6aENPz1g8AWM_oIo</recordid><startdate>20020701</startdate><enddate>20020701</enddate><creator>Imai, Yuzuru</creator><creator>Soda, Mariko</creator><creator>Hatakeyama, Shigetsugu</creator><creator>Akagi, Takumi</creator><creator>Hashikawa, Tsutomu</creator><creator>Nakayama, Kei-Ichi</creator><creator>Takahashi, Ryosuke</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><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>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20020701</creationdate><title>CHIP Is Associated with Parkin, a Gene Responsible for Familial Parkinson's Disease, and Enhances Its Ubiquitin Ligase Activity</title><author>Imai, Yuzuru ; Soda, Mariko ; Hatakeyama, Shigetsugu ; Akagi, Takumi ; Hashikawa, Tsutomu ; Nakayama, Kei-Ichi ; Takahashi, Ryosuke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-4e08c22ec623a659b4d73adc669a0e50081bfdf5c80c73185a9715a73dd2ee283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Blotting, Western</topic><topic>Cell Death</topic><topic>Endoplasmic Reticulum - metabolism</topic><topic>Gene Expression Regulation</topic><topic>HSP70 Heat-Shock Proteins - metabolism</topic><topic>Humans</topic><topic>Ligases - genetics</topic><topic>Ligases - metabolism</topic><topic>Macromolecular Substances</topic><topic>Male</topic><topic>Mice</topic><topic>Models, Biological</topic><topic>Parkinsonian Disorders - enzymology</topic><topic>Parkinsonian Disorders - genetics</topic><topic>Parkinsonian Disorders - pathology</topic><topic>Protein Binding</topic><topic>Protein Folding</topic><topic>Protein Transport</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Substantia Nigra - ultrastructure</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><topic>Ubiquitin-Protein Ligases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Imai, Yuzuru</creatorcontrib><creatorcontrib>Soda, Mariko</creatorcontrib><creatorcontrib>Hatakeyama, Shigetsugu</creatorcontrib><creatorcontrib>Akagi, Takumi</creatorcontrib><creatorcontrib>Hashikawa, Tsutomu</creatorcontrib><creatorcontrib>Nakayama, Kei-Ichi</creatorcontrib><creatorcontrib>Takahashi, Ryosuke</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Imai, Yuzuru</au><au>Soda, Mariko</au><au>Hatakeyama, Shigetsugu</au><au>Akagi, Takumi</au><au>Hashikawa, Tsutomu</au><au>Nakayama, Kei-Ichi</au><au>Takahashi, Ryosuke</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CHIP Is Associated with Parkin, a Gene Responsible for Familial Parkinson's Disease, and Enhances Its Ubiquitin Ligase Activity</atitle><jtitle>Molecular cell</jtitle><addtitle>Mol Cell</addtitle><date>2002-07-01</date><risdate>2002</risdate><volume>10</volume><issue>1</issue><spage>55</spage><epage>67</epage><pages>55-67</pages><issn>1097-2765</issn><eissn>1097-4164</eissn><abstract>Unfolded Pael receptor (Pael-R) is a substrate of the E3 ubiquitin ligase Parkin. Accumulation of Pael-R in the endoplasmic reticulum (ER) of dopaminergic neurons induces ER stress leading to neurodegeneration. Here, we show that CHIP, Hsp70, Parkin, and Pael-R formed a complex in vitro and in vivo. The amount of CHIP in the complex was increased during ER stress. CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. Moreover, CHIP enhanced Parkin-mediated in vitro ubiquitination of Pael-R in the absence of Hsp70. Furthermore, CHIP enhanced the ability of Parkin to inhibit cell death induced by Pael-R. Taken together, these results indicate that CHIP is a mammalian E4-like molecule that positively regulates Parkin E3 activity.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12150907</pmid><doi>10.1016/S1097-2765(02)00583-X</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Blotting, Western Cell Death Endoplasmic Reticulum - metabolism Gene Expression Regulation HSP70 Heat-Shock Proteins - metabolism Humans Ligases - genetics Ligases - metabolism Macromolecular Substances Male Mice Models, Biological Parkinsonian Disorders - enzymology Parkinsonian Disorders - genetics Parkinsonian Disorders - pathology Protein Binding Protein Folding Protein Transport Rats Rats, Wistar Substantia Nigra - ultrastructure Transfection Tumor Cells, Cultured Ubiquitin-Protein Ligases |
| title | CHIP Is Associated with Parkin, a Gene Responsible for Familial Parkinson's Disease, and Enhances Its Ubiquitin Ligase Activity |
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