Presenilins Are Processed by Caspase-type Proteases
Presenilin 1 (PS1) and presenilin 2 (PS2) are endoproteolytically processed in vivo and in cell transfectants to yield 27–35-kDa N-terminal and 15–24-kDa C-terminal fragments. We have studied the cleavage of PS1 and PS2 in transiently and stably transfected hamster kidney and mouse and human neurobl...
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| Veröffentlicht in: | The Journal of biological chemistry 1997-08, Vol.272 (33), p.20655-20659 |
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| container_issue | 33 |
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| container_title | The Journal of biological chemistry |
| container_volume | 272 |
| creator | Loetscher, Hansruedi Deuschle, Ulrich Brockhaus, Manfred Reinhardt, Dieter Nelboeck, Peter Mous, Jan Grünberg, Jürgen Haass, Christian Jacobsen, Helmut |
| description | Presenilin 1 (PS1) and presenilin 2 (PS2) are endoproteolytically processed in vivo and in cell transfectants to yield 27–35-kDa N-terminal and 15–24-kDa C-terminal fragments. We have studied the cleavage of PS1 and PS2 in transiently and stably transfected hamster kidney and mouse and human neuroblastoma cells by immunoblot and pulse-chase experiments. C-terminal fragments were isolated by affinity chromatography and SDS-polyacrylamide gel electrophoresis and sequenced. The processing sites identified in PS1 and PS2 (Asp345/Ser346 and Asp329/Ser330, respectively) are typical for caspase-type proteases. Specific caspase inhibitors and cleavage site mutations confirmed the involvement of caspase(s) in PS1 and PS2 processing in cell transfectants. Fluorescent peptide substrates carrying the PS-identified cleavage sites were hydrolyzed by proteolytic activity from mouse brain. The PS2-derived peptide substrate was also cleaved by recombinant human caspase-3. Additional processing of PS2 by non-caspase-type proteases was also observed. |
| doi_str_mv | 10.1074/jbc.272.33.20655 |
| format | Article |
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Additional processing of PS2 by non-caspase-type proteases was also observed.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.272.33.20655</identifier><identifier>PMID: 9252383</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acid Sequence ; Animals ; Caspase 3 ; Caspases ; Cricetinae ; Cysteine Endopeptidases - physiology ; Humans ; Membrane Proteins - metabolism ; Mice ; Molecular Sequence Data ; Presenilin-1 ; Presenilin-2</subject><ispartof>The Journal of biological chemistry, 1997-08, Vol.272 (33), p.20655-20659</ispartof><rights>1997 © 1997 ASBMB. 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Additional processing of PS2 by non-caspase-type proteases was also observed.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Caspase 3</subject><subject>Caspases</subject><subject>Cricetinae</subject><subject>Cysteine Endopeptidases - physiology</subject><subject>Humans</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>Presenilin-1</subject><subject>Presenilin-2</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtLwzAcx4Moc07vXoQexFtrXm1Tb2P4AsEdFLyFNPnVZfRl0in7743r8CD4u4Rfvg9-fBA6JzghOOfX61InNKcJYwnFWZoeoCnBgsUsJW-HaIoxJXFBU3GMTrxf4zC8IBM0CX-UCTZFbOnAQ2tr2_po7iBauk6D92CichstlO-Vh3jY9jtlgLD5U3RUqdrD2f6dode725fFQ_z0fP-4mD_FmpNsiAllvABqKGDOS0IrpTApBaECwLBCKFpmKTGiMowbYnKohMCU50RVPM8yzWboauztXfexAT_IxnoNda1a6DZe5gUpWMppMOLRqF3nvYNK9s42ym0lwfKHkwycZOAkGZM7TiFyse_elA2Y38AeTNAvR31l31df1oEsbadX0PytuRltEDh8WnDSawutBhMiepCms__f8A0PFIGg</recordid><startdate>19970815</startdate><enddate>19970815</enddate><creator>Loetscher, Hansruedi</creator><creator>Deuschle, Ulrich</creator><creator>Brockhaus, Manfred</creator><creator>Reinhardt, Dieter</creator><creator>Nelboeck, Peter</creator><creator>Mous, Jan</creator><creator>Grünberg, Jürgen</creator><creator>Haass, Christian</creator><creator>Jacobsen, Helmut</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</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>7X8</scope></search><sort><creationdate>19970815</creationdate><title>Presenilins Are Processed by Caspase-type Proteases</title><author>Loetscher, Hansruedi ; Deuschle, Ulrich ; Brockhaus, Manfred ; Reinhardt, Dieter ; Nelboeck, Peter ; Mous, Jan ; Grünberg, Jürgen ; Haass, Christian ; Jacobsen, Helmut</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-12349e2d2e044b12faa01b8128eed398a2b651d8fd34d1d7ef8802471af4766c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Caspase 3</topic><topic>Caspases</topic><topic>Cricetinae</topic><topic>Cysteine Endopeptidases - physiology</topic><topic>Humans</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice</topic><topic>Molecular Sequence Data</topic><topic>Presenilin-1</topic><topic>Presenilin-2</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Loetscher, Hansruedi</creatorcontrib><creatorcontrib>Deuschle, Ulrich</creatorcontrib><creatorcontrib>Brockhaus, Manfred</creatorcontrib><creatorcontrib>Reinhardt, Dieter</creatorcontrib><creatorcontrib>Nelboeck, Peter</creatorcontrib><creatorcontrib>Mous, Jan</creatorcontrib><creatorcontrib>Grünberg, Jürgen</creatorcontrib><creatorcontrib>Haass, Christian</creatorcontrib><creatorcontrib>Jacobsen, Helmut</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>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Loetscher, Hansruedi</au><au>Deuschle, Ulrich</au><au>Brockhaus, Manfred</au><au>Reinhardt, Dieter</au><au>Nelboeck, Peter</au><au>Mous, Jan</au><au>Grünberg, Jürgen</au><au>Haass, Christian</au><au>Jacobsen, Helmut</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Presenilins Are Processed by Caspase-type Proteases</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1997-08-15</date><risdate>1997</risdate><volume>272</volume><issue>33</issue><spage>20655</spage><epage>20659</epage><pages>20655-20659</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Presenilin 1 (PS1) and presenilin 2 (PS2) are endoproteolytically processed in vivo and in cell transfectants to yield 27–35-kDa N-terminal and 15–24-kDa C-terminal fragments. 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Additional processing of PS2 by non-caspase-type proteases was also observed.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>9252383</pmid><doi>10.1074/jbc.272.33.20655</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0021-9258 |
| ispartof | The Journal of biological chemistry, 1997-08, Vol.272 (33), p.20655-20659 |
| issn | 0021-9258 1083-351X |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Amino Acid Sequence Animals Caspase 3 Caspases Cricetinae Cysteine Endopeptidases - physiology Humans Membrane Proteins - metabolism Mice Molecular Sequence Data Presenilin-1 Presenilin-2 |
| title | Presenilins Are Processed by Caspase-type Proteases |
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