Degradation of BACE by the ubiquitin‐proteasome pathway
ABSTRACT The amyloid β protein (Aβ) is derived from β‐amyloid precursor protein (APP). Cleavage of APP by β‐secretase generates a C‐terminal fragment (APPCTFβ or C99), which is subsequently cleaved by γ‐secretase to produce Aβ. BACE (or BACE1), the major β‐secretase involved in cleaving APP, has bee...
Gespeichert in:
| Veröffentlicht in: | The FASEB journal 2004-10, Vol.18 (13), p.1571-1573 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1573 |
|---|---|
| container_issue | 13 |
| container_start_page | 1571 |
| container_title | The FASEB journal |
| container_volume | 18 |
| creator | Qing, Hong Zhou, Weihui A. Christensen, Michelle Sun, Xiulian Tong, Yigang Song, Weihong |
| description | ABSTRACT
The amyloid β protein (Aβ) is derived from β‐amyloid precursor protein (APP). Cleavage of APP by β‐secretase generates a C‐terminal fragment (APPCTFβ or C99), which is subsequently cleaved by γ‐secretase to produce Aβ. BACE (or BACE1), the major β‐secretase involved in cleaving APP, has been identified as a Type 1 membrane‐associated aspartyl protease. In this study, we found that treatment with proteasome inhibitors resulted in an increase in APP C99 levels, suggesting that APP processing at the β‐secretase site may be affected by the ubiquitin‐proteasome pathway. To investigate whether the degradation of BACE is mediated by the proteasome pathway, cells stably transfected with BACE were treated with lactacystin. We found that BACE protein degradation was inhibited by lactacystin in a time‐ and dose‐dependent manner. Non‐proteasome protease inhibitors had no effect on BACE degradation. BACE protein is ubiquitinated. Furthermore, lactacystin increased APP C99 production and Aβ generation. Our data demonstrate that the degradation of BACE proteins and APP processing are regulated by the ubiquitin‐proteasome pathway. |
| doi_str_mv | 10.1096/fj.04-1994fje |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_66936055</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>66936055</sourcerecordid><originalsourceid>FETCH-LOGICAL-c445E-e860fdd2c53c7fed5b0997237786f741d71ec3b9cea84f5019291f3728c2d3e43</originalsourceid><addsrcrecordid>eNp9kL1OwzAURi0EoqUwsqJMbCl2_JOYrZQEqCoxALPlONc0Udq0caIqG4_AM_IkpGokNqarKx0dfToIXRM8JViKO1tMMfOJlMwWcILGhFPsi0jgUzTGkQx8IWg0QhfOFRhjgok4RyPCg0gyTsZIPsJnrTPd5NXGq6z3MJvHXtp5zQq8Ns13bd7km5-v721dNaBdtQZvq5vVXneX6Mzq0sHVcCfoI4nf58_-8vXpZT5b-oYxHvvQT7FZFhhOTWgh4ymWMgxoGEbChoxkIQFDU2lAR8xyTGQgiaVhEJkgo8DoBN0evf2EXQuuUevcGShLvYGqdUoISQXmvAf9I2jqyrkarNrW-VrXnSJYHVopWyjM1NCq528GcZuuIfujhzg9cH8E9nkJ3f82lbw9BMkCs8OfLGL6C4umd3Q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>66936055</pqid></control><display><type>article</type><title>Degradation of BACE by the ubiquitin‐proteasome pathway</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Alma/SFX Local Collection</source><creator>Qing, Hong ; Zhou, Weihui ; A. Christensen, Michelle ; Sun, Xiulian ; Tong, Yigang ; Song, Weihong</creator><creatorcontrib>Qing, Hong ; Zhou, Weihui ; A. Christensen, Michelle ; Sun, Xiulian ; Tong, Yigang ; Song, Weihong</creatorcontrib><description>ABSTRACT
The amyloid β protein (Aβ) is derived from β‐amyloid precursor protein (APP). Cleavage of APP by β‐secretase generates a C‐terminal fragment (APPCTFβ or C99), which is subsequently cleaved by γ‐secretase to produce Aβ. BACE (or BACE1), the major β‐secretase involved in cleaving APP, has been identified as a Type 1 membrane‐associated aspartyl protease. In this study, we found that treatment with proteasome inhibitors resulted in an increase in APP C99 levels, suggesting that APP processing at the β‐secretase site may be affected by the ubiquitin‐proteasome pathway. To investigate whether the degradation of BACE is mediated by the proteasome pathway, cells stably transfected with BACE were treated with lactacystin. We found that BACE protein degradation was inhibited by lactacystin in a time‐ and dose‐dependent manner. Non‐proteasome protease inhibitors had no effect on BACE degradation. BACE protein is ubiquitinated. Furthermore, lactacystin increased APP C99 production and Aβ generation. Our data demonstrate that the degradation of BACE proteins and APP processing are regulated by the ubiquitin‐proteasome pathway.</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.04-1994fje</identifier><identifier>PMID: 15289451</identifier><language>eng</language><publisher>United States: Federation of American Societies for Experimental Biology</publisher><subject>Acetylcysteine - analogs & derivatives ; Acetylcysteine - pharmacology ; Alzheimer’s Disease ; Amyloid beta-Peptides - genetics ; Amyloid beta-Peptides - metabolism ; Amyloid beta-Protein Precursor - genetics ; Amyloid beta-Protein Precursor - metabolism ; Amyloid Precursor Protein Secretases ; APP ; Aspartic Acid Endopeptidases - genetics ; Aspartic Acid Endopeptidases - metabolism ; Cell Line ; Cell Line, Tumor ; Endopeptidases - genetics ; Endopeptidases - metabolism ; Humans ; Proteasome Endopeptidase Complex - metabolism ; Proteasome Inhibitors ; Protein Processing, Post-Translational - drug effects ; Ubiquitin - genetics ; Ubiquitin - metabolism</subject><ispartof>The FASEB journal, 2004-10, Vol.18 (13), p.1571-1573</ispartof><rights>FASEB</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445E-e860fdd2c53c7fed5b0997237786f741d71ec3b9cea84f5019291f3728c2d3e43</citedby><cites>FETCH-LOGICAL-c445E-e860fdd2c53c7fed5b0997237786f741d71ec3b9cea84f5019291f3728c2d3e43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1096%2Ffj.04-1994fje$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1096%2Ffj.04-1994fje$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15289451$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qing, Hong</creatorcontrib><creatorcontrib>Zhou, Weihui</creatorcontrib><creatorcontrib>A. Christensen, Michelle</creatorcontrib><creatorcontrib>Sun, Xiulian</creatorcontrib><creatorcontrib>Tong, Yigang</creatorcontrib><creatorcontrib>Song, Weihong</creatorcontrib><title>Degradation of BACE by the ubiquitin‐proteasome pathway</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>ABSTRACT
The amyloid β protein (Aβ) is derived from β‐amyloid precursor protein (APP). Cleavage of APP by β‐secretase generates a C‐terminal fragment (APPCTFβ or C99), which is subsequently cleaved by γ‐secretase to produce Aβ. BACE (or BACE1), the major β‐secretase involved in cleaving APP, has been identified as a Type 1 membrane‐associated aspartyl protease. In this study, we found that treatment with proteasome inhibitors resulted in an increase in APP C99 levels, suggesting that APP processing at the β‐secretase site may be affected by the ubiquitin‐proteasome pathway. To investigate whether the degradation of BACE is mediated by the proteasome pathway, cells stably transfected with BACE were treated with lactacystin. We found that BACE protein degradation was inhibited by lactacystin in a time‐ and dose‐dependent manner. Non‐proteasome protease inhibitors had no effect on BACE degradation. BACE protein is ubiquitinated. Furthermore, lactacystin increased APP C99 production and Aβ generation. Our data demonstrate that the degradation of BACE proteins and APP processing are regulated by the ubiquitin‐proteasome pathway.</description><subject>Acetylcysteine - analogs & derivatives</subject><subject>Acetylcysteine - pharmacology</subject><subject>Alzheimer’s Disease</subject><subject>Amyloid beta-Peptides - genetics</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Amyloid beta-Protein Precursor - genetics</subject><subject>Amyloid beta-Protein Precursor - metabolism</subject><subject>Amyloid Precursor Protein Secretases</subject><subject>APP</subject><subject>Aspartic Acid Endopeptidases - genetics</subject><subject>Aspartic Acid Endopeptidases - metabolism</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Endopeptidases - genetics</subject><subject>Endopeptidases - metabolism</subject><subject>Humans</subject><subject>Proteasome Endopeptidase Complex - metabolism</subject><subject>Proteasome Inhibitors</subject><subject>Protein Processing, Post-Translational - drug effects</subject><subject>Ubiquitin - genetics</subject><subject>Ubiquitin - metabolism</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kL1OwzAURi0EoqUwsqJMbCl2_JOYrZQEqCoxALPlONc0Udq0caIqG4_AM_IkpGokNqarKx0dfToIXRM8JViKO1tMMfOJlMwWcILGhFPsi0jgUzTGkQx8IWg0QhfOFRhjgok4RyPCg0gyTsZIPsJnrTPd5NXGq6z3MJvHXtp5zQq8Ns13bd7km5-v721dNaBdtQZvq5vVXneX6Mzq0sHVcCfoI4nf58_-8vXpZT5b-oYxHvvQT7FZFhhOTWgh4ymWMgxoGEbChoxkIQFDU2lAR8xyTGQgiaVhEJkgo8DoBN0evf2EXQuuUevcGShLvYGqdUoISQXmvAf9I2jqyrkarNrW-VrXnSJYHVopWyjM1NCq528GcZuuIfujhzg9cH8E9nkJ3f82lbw9BMkCs8OfLGL6C4umd3Q</recordid><startdate>200410</startdate><enddate>200410</enddate><creator>Qing, Hong</creator><creator>Zhou, Weihui</creator><creator>A. Christensen, Michelle</creator><creator>Sun, Xiulian</creator><creator>Tong, Yigang</creator><creator>Song, Weihong</creator><general>Federation of American Societies for Experimental Biology</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>200410</creationdate><title>Degradation of BACE by the ubiquitin‐proteasome pathway</title><author>Qing, Hong ; Zhou, Weihui ; A. Christensen, Michelle ; Sun, Xiulian ; Tong, Yigang ; Song, Weihong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445E-e860fdd2c53c7fed5b0997237786f741d71ec3b9cea84f5019291f3728c2d3e43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Acetylcysteine - analogs & derivatives</topic><topic>Acetylcysteine - pharmacology</topic><topic>Alzheimer’s Disease</topic><topic>Amyloid beta-Peptides - genetics</topic><topic>Amyloid beta-Peptides - metabolism</topic><topic>Amyloid beta-Protein Precursor - genetics</topic><topic>Amyloid beta-Protein Precursor - metabolism</topic><topic>Amyloid Precursor Protein Secretases</topic><topic>APP</topic><topic>Aspartic Acid Endopeptidases - genetics</topic><topic>Aspartic Acid Endopeptidases - metabolism</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>Endopeptidases - genetics</topic><topic>Endopeptidases - metabolism</topic><topic>Humans</topic><topic>Proteasome Endopeptidase Complex - metabolism</topic><topic>Proteasome Inhibitors</topic><topic>Protein Processing, Post-Translational - drug effects</topic><topic>Ubiquitin - genetics</topic><topic>Ubiquitin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qing, Hong</creatorcontrib><creatorcontrib>Zhou, Weihui</creatorcontrib><creatorcontrib>A. Christensen, Michelle</creatorcontrib><creatorcontrib>Sun, Xiulian</creatorcontrib><creatorcontrib>Tong, Yigang</creatorcontrib><creatorcontrib>Song, Weihong</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 FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qing, Hong</au><au>Zhou, Weihui</au><au>A. Christensen, Michelle</au><au>Sun, Xiulian</au><au>Tong, Yigang</au><au>Song, Weihong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Degradation of BACE by the ubiquitin‐proteasome pathway</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2004-10</date><risdate>2004</risdate><volume>18</volume><issue>13</issue><spage>1571</spage><epage>1573</epage><pages>1571-1573</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>ABSTRACT
The amyloid β protein (Aβ) is derived from β‐amyloid precursor protein (APP). Cleavage of APP by β‐secretase generates a C‐terminal fragment (APPCTFβ or C99), which is subsequently cleaved by γ‐secretase to produce Aβ. BACE (or BACE1), the major β‐secretase involved in cleaving APP, has been identified as a Type 1 membrane‐associated aspartyl protease. In this study, we found that treatment with proteasome inhibitors resulted in an increase in APP C99 levels, suggesting that APP processing at the β‐secretase site may be affected by the ubiquitin‐proteasome pathway. To investigate whether the degradation of BACE is mediated by the proteasome pathway, cells stably transfected with BACE were treated with lactacystin. We found that BACE protein degradation was inhibited by lactacystin in a time‐ and dose‐dependent manner. Non‐proteasome protease inhibitors had no effect on BACE degradation. BACE protein is ubiquitinated. Furthermore, lactacystin increased APP C99 production and Aβ generation. Our data demonstrate that the degradation of BACE proteins and APP processing are regulated by the ubiquitin‐proteasome pathway.</abstract><cop>United States</cop><pub>Federation of American Societies for Experimental Biology</pub><pmid>15289451</pmid><doi>10.1096/fj.04-1994fje</doi><tpages>21</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0892-6638 |
| ispartof | The FASEB journal, 2004-10, Vol.18 (13), p.1571-1573 |
| issn | 0892-6638 1530-6860 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_66936055 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Alma/SFX Local Collection |
| subjects | Acetylcysteine - analogs & derivatives Acetylcysteine - pharmacology Alzheimer’s Disease Amyloid beta-Peptides - genetics Amyloid beta-Peptides - metabolism Amyloid beta-Protein Precursor - genetics Amyloid beta-Protein Precursor - metabolism Amyloid Precursor Protein Secretases APP Aspartic Acid Endopeptidases - genetics Aspartic Acid Endopeptidases - metabolism Cell Line Cell Line, Tumor Endopeptidases - genetics Endopeptidases - metabolism Humans Proteasome Endopeptidase Complex - metabolism Proteasome Inhibitors Protein Processing, Post-Translational - drug effects Ubiquitin - genetics Ubiquitin - metabolism |
| title | Degradation of BACE by the ubiquitin‐proteasome pathway |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T05%3A30%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Degradation%20of%20BACE%20by%20the%20ubiquitin%E2%80%90proteasome%20pathway&rft.jtitle=The%20FASEB%20journal&rft.au=Qing,%20Hong&rft.date=2004-10&rft.volume=18&rft.issue=13&rft.spage=1571&rft.epage=1573&rft.pages=1571-1573&rft.issn=0892-6638&rft.eissn=1530-6860&rft_id=info:doi/10.1096/fj.04-1994fje&rft_dat=%3Cproquest_cross%3E66936055%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=66936055&rft_id=info:pmid/15289451&rfr_iscdi=true |