The Hrd1p ligase complex forms a linchpin between ER-lumenal substrate selection and Cdc48p recruitment
Misfolded proteins of the endoplasmic reticulum (ER) are targeted to the cytoplasm for proteasomal degradation. Key components of this process are ER membrane‐bound ubiquitin ligases. These ligases associate with the cytoplasmic AAA‐ATPase Cdc48p/p97, which is thought to support the release of malfo...
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| Veröffentlicht in: | The EMBO journal 2006-05, Vol.25 (9), p.1827-1835 |
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| creator | Gauss, Robert Sommer, Thomas Jarosch, Ernst |
| description | Misfolded proteins of the endoplasmic reticulum (ER) are targeted to the cytoplasm for proteasomal degradation. Key components of this process are ER membrane‐bound ubiquitin ligases. These ligases associate with the cytoplasmic AAA‐ATPase Cdc48p/p97, which is thought to support the release of malfolded proteins from the ER. Here, we characterize a yeast protein complex containing the ubiquitin ligase Hrd1p and the ER membrane proteins Hrd3p and Der1p. Hrd3p binds malfolded proteins in the ER lumen enabling their delivery to downstream components. Therefore, we propose that Hrd3p acts as a substrate recruitment factor for the Hrd1p ligase complex. Hrd3p function is also required for the association of Cdc48p with Hrd1p. Moreover, our data demonstrate that recruitment of Cdc48p depends on substrate processing by the Hrd1p ligase complex. Thus, the Hrd1p ligase complex unites substrate selection in the ER lumen and polyubiquitination in the cytoplasm and links these processes to the release of ER proteins via the Cdc48p complex. |
| doi_str_mv | 10.1038/sj.emboj.7601088 |
| format | Article |
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Thus, the Hrd1p ligase complex unites substrate selection in the ER lumen and polyubiquitination in the cytoplasm and links these processes to the release of ER proteins via the Cdc48p complex.</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1038/sj.emboj.7601088</identifier><identifier>PMID: 16619026</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Adenosine Triphosphatases ; Catalysis ; Cdc48/p97 ; Cell Cycle Proteins - metabolism ; EMBO20 ; EMBO31 ; Endoplasmic Reticulum - enzymology ; Enzymes ; ERAD ; Hrd1 ; Hrd3 ; Membrane Glycoproteins - metabolism ; Membrane Proteins - metabolism ; Membranes ; protein degradation ; Protein Folding ; Proteins ; Saccharomyces cerevisiae - enzymology ; Saccharomyces cerevisiae Proteins - metabolism ; Substrate Specificity ; Substrates ; Ubiquitin - metabolism ; Ubiquitin-Conjugating Enzymes - metabolism ; Ubiquitin-Protein Ligases - metabolism ; Valosin Containing Protein ; Yeast ; Yeasts</subject><ispartof>The EMBO journal, 2006-05, Vol.25 (9), p.1827-1835</ispartof><rights>European Molecular Biology Organization 2006</rights><rights>Copyright © 2006 European Molecular Biology Organization</rights><rights>Copyright Nature Publishing Group May 3, 2006</rights><rights>Copyright © 2006, European Molecular Biology Organization 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6488-933d667c55f5410e504cc29d062221ed603a4ce7c077144167de402ee2858bc3</citedby><cites>FETCH-LOGICAL-c6488-933d667c55f5410e504cc29d062221ed603a4ce7c077144167de402ee2858bc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1456945/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1456945/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,41096,42165,45550,45551,46384,46808,51551,53766,53768</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.1038/sj.emboj.7601088$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16619026$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gauss, Robert</creatorcontrib><creatorcontrib>Sommer, Thomas</creatorcontrib><creatorcontrib>Jarosch, Ernst</creatorcontrib><title>The Hrd1p ligase complex forms a linchpin between ER-lumenal substrate selection and Cdc48p recruitment</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>Misfolded proteins of the endoplasmic reticulum (ER) are targeted to the cytoplasm for proteasomal degradation. Key components of this process are ER membrane‐bound ubiquitin ligases. These ligases associate with the cytoplasmic AAA‐ATPase Cdc48p/p97, which is thought to support the release of malfolded proteins from the ER. Here, we characterize a yeast protein complex containing the ubiquitin ligase Hrd1p and the ER membrane proteins Hrd3p and Der1p. Hrd3p binds malfolded proteins in the ER lumen enabling their delivery to downstream components. Therefore, we propose that Hrd3p acts as a substrate recruitment factor for the Hrd1p ligase complex. Hrd3p function is also required for the association of Cdc48p with Hrd1p. Moreover, our data demonstrate that recruitment of Cdc48p depends on substrate processing by the Hrd1p ligase complex. Thus, the Hrd1p ligase complex unites substrate selection in the ER lumen and polyubiquitination in the cytoplasm and links these processes to the release of ER proteins via the Cdc48p complex.</description><subject>Adenosine Triphosphatases</subject><subject>Catalysis</subject><subject>Cdc48/p97</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>EMBO20</subject><subject>EMBO31</subject><subject>Endoplasmic Reticulum - enzymology</subject><subject>Enzymes</subject><subject>ERAD</subject><subject>Hrd1</subject><subject>Hrd3</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Membrane Proteins - metabolism</subject><subject>Membranes</subject><subject>protein degradation</subject><subject>Protein Folding</subject><subject>Proteins</subject><subject>Saccharomyces cerevisiae - enzymology</subject><subject>Saccharomyces cerevisiae Proteins - metabolism</subject><subject>Substrate Specificity</subject><subject>Substrates</subject><subject>Ubiquitin - metabolism</subject><subject>Ubiquitin-Conjugating Enzymes - metabolism</subject><subject>Ubiquitin-Protein Ligases - metabolism</subject><subject>Valosin Containing Protein</subject><subject>Yeast</subject><subject>Yeasts</subject><issn>0261-4189</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkUtvEzEUhS0EoiGwZ4UsFuwm-Hr8mg0SRKGlakGgSFRsLMdzk0yYF_YMbf89hkRtQUJdWfL9zrmPQ8hzYDNguXkddzNsVt1uphUDZswDMgGhWMaZlg_JhHEFmQBTHJEnMe4YY9JoeEyOQCkoUnVCNsst0pNQQk_rauMiUt81fY1XdN2FJlKXvlu_7auWrnC4RGzp4ktWjw22rqZxXMUhuAFpxBr9UHUtdW1J56UXpqcBfRirIbHDU_Jo7eqIzw7vlCzfL5bzk-zs0_GH-duzzCthTFbkeamU9lKupQCGkgnveVEyxTkHLBXLnfCoPdMahAClSxSMI3IjzcrnU_Jmb9uPqwZLnzoHV9s-VI0L17Zzlf270lZbu-l-WhBSFUImg1cHg9D9GDEOtqmix7p2LXZjtEoXOZda3QuCBgOQ6wS-_AfcdWNI10tMIbnSPEU5JWwP-dDFGHB9MzIw-ztqG3f2T9T2EHWSvLi76q3gkG0Cij1wWdV4fa-hXZy_O701h702Jlm7wXBn6P8PlO01VRzw6qafC9_T1XIt7dePx5ZfnH87_SwurMx_ATCG2Cs</recordid><startdate>20060503</startdate><enddate>20060503</enddate><creator>Gauss, Robert</creator><creator>Sommer, Thomas</creator><creator>Jarosch, Ernst</creator><general>John Wiley & Sons, Ltd</general><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><scope>BSCLL</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PCBAR</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20060503</creationdate><title>The Hrd1p ligase complex forms a linchpin between ER-lumenal substrate selection and Cdc48p recruitment</title><author>Gauss, Robert ; Sommer, Thomas ; Jarosch, Ernst</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6488-933d667c55f5410e504cc29d062221ed603a4ce7c077144167de402ee2858bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adenosine Triphosphatases</topic><topic>Catalysis</topic><topic>Cdc48/p97</topic><topic>Cell Cycle Proteins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Gauss, Robert</au><au>Sommer, Thomas</au><au>Jarosch, Ernst</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Hrd1p ligase complex forms a linchpin between ER-lumenal substrate selection and Cdc48p recruitment</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>2006-05-03</date><risdate>2006</risdate><volume>25</volume><issue>9</issue><spage>1827</spage><epage>1835</epage><pages>1827-1835</pages><issn>0261-4189</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><abstract>Misfolded proteins of the endoplasmic reticulum (ER) are targeted to the cytoplasm for proteasomal degradation. Key components of this process are ER membrane‐bound ubiquitin ligases. These ligases associate with the cytoplasmic AAA‐ATPase Cdc48p/p97, which is thought to support the release of malfolded proteins from the ER. Here, we characterize a yeast protein complex containing the ubiquitin ligase Hrd1p and the ER membrane proteins Hrd3p and Der1p. Hrd3p binds malfolded proteins in the ER lumen enabling their delivery to downstream components. Therefore, we propose that Hrd3p acts as a substrate recruitment factor for the Hrd1p ligase complex. Hrd3p function is also required for the association of Cdc48p with Hrd1p. Moreover, our data demonstrate that recruitment of Cdc48p depends on substrate processing by the Hrd1p ligase complex. Thus, the Hrd1p ligase complex unites substrate selection in the ER lumen and polyubiquitination in the cytoplasm and links these processes to the release of ER proteins via the Cdc48p complex.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>16619026</pmid><doi>10.1038/sj.emboj.7601088</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenosine Triphosphatases Catalysis Cdc48/p97 Cell Cycle Proteins - metabolism EMBO20 EMBO31 Endoplasmic Reticulum - enzymology Enzymes ERAD Hrd1 Hrd3 Membrane Glycoproteins - metabolism Membrane Proteins - metabolism Membranes protein degradation Protein Folding Proteins Saccharomyces cerevisiae - enzymology Saccharomyces cerevisiae Proteins - metabolism Substrate Specificity Substrates Ubiquitin - metabolism Ubiquitin-Conjugating Enzymes - metabolism Ubiquitin-Protein Ligases - metabolism Valosin Containing Protein Yeast Yeasts |
| title | The Hrd1p ligase complex forms a linchpin between ER-lumenal substrate selection and Cdc48p recruitment |
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