PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation
The role of the endoplasmic reticulum stress-regulated kinase, PERK, in mammary gland function was assessed through generation of a targeted deletion in mammary epithelium. Characterization revealed that PERK is required for functional maturation of milk-secreting mammary epithelial cells. PERK-depe...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2008-10, Vol.105 (42), p.16314-16319 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 16319 |
|---|---|
| container_issue | 42 |
| container_start_page | 16314 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 105 |
| creator | Bobrovnikova-Marjon, Ekaterina Hatzivassiliou, Georgia Grigoriadou, Christina Romero, Margarita Cavener, Douglas R Thompson, Craig B Diehl, J. Alan |
| description | The role of the endoplasmic reticulum stress-regulated kinase, PERK, in mammary gland function was assessed through generation of a targeted deletion in mammary epithelium. Characterization revealed that PERK is required for functional maturation of milk-secreting mammary epithelial cells. PERK-dependent signaling contributes to lipogenic differentiation in mammary epithelium, and perk deletion inhibits the sustained expression of lipogenic enzymes FAS, ACL, and SCD1. As a result, mammary tissue has reduced lipid content and the milk produced has altered lipid composition, resulting in attenuated pup growth. Consistent with PERK-dependent regulation of the lipogenic pathway, loss of PERK inhibits expression of FAS, ACL, and SCD1 in immortalized murine embryonic fibroblasts when cultured under conditions favoring adipocyte differentiation. These findings implicate PERK as a physiologically relevant regulator of the lipogenic pathway. |
| doi_str_mv | 10.1073/pnas.0808517105 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1073_pnas_0808517105</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>25465088</jstor_id><sourcerecordid>25465088</sourcerecordid><originalsourceid>FETCH-LOGICAL-c589t-77ce4c390a0f739a6500f9314dddac34f8787dfe980b9dc18dca4009b28d0ccb3</originalsourceid><addsrcrecordid>eNqFkc1v1DAQxS0EoqVw5gRYHJA4pB3HdmJfkFBVPkQlENCz5fVH8CqJUzup6H-Pw666wIWTNZ7fPM2bh9BTAqcEWno2jTqfggDBSUuA30PHBCSpGibhPjoGqNtKsJodoUc5bwFAcgEP0RERgtesgWM0fLn4-qmybnKjdeOMk-uWXs8hjjh63Icpdm50OWRslxTGDg9xyQ4Pehh0usVdr0eLrbtxfZyGVWCttS1z5nZ22AbvXSr_4bfmY_TA6z67J_v3BF29u_h-_qG6_Pz-4_nby8pwIeeqbY1jhkrQ4FsqdcMBvKSEWWu1ocyLVrTWOylgI60hwhrNirlNLSwYs6En6M1Od1o2g7OmLJB0r6YU1q1V1EH93RnDD9XFG1XzFqTkReDVXiDF68XlWQ0hG9cXu64cQDWykRIkLeDLf8BtXNJYzKkaCBWMy7pAZzvIpJhzcv5uEwJqzVGtOapDjmXi-Z8GDvw-uALgPbBOHuS4YrUiTblVQV7_B1F-6fvZ_ZwL-2zHbvMc0x1cc1ZuL0Tpv9j1vY5KdylkdfVtNQiEt41glP4Ctw7IAA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>201384592</pqid></control><display><type>article</type><title>PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation</title><source>Jstor Complete Legacy</source><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Bobrovnikova-Marjon, Ekaterina ; Hatzivassiliou, Georgia ; Grigoriadou, Christina ; Romero, Margarita ; Cavener, Douglas R ; Thompson, Craig B ; Diehl, J. Alan</creator><creatorcontrib>Bobrovnikova-Marjon, Ekaterina ; Hatzivassiliou, Georgia ; Grigoriadou, Christina ; Romero, Margarita ; Cavener, Douglas R ; Thompson, Craig B ; Diehl, J. Alan</creatorcontrib><description>The role of the endoplasmic reticulum stress-regulated kinase, PERK, in mammary gland function was assessed through generation of a targeted deletion in mammary epithelium. Characterization revealed that PERK is required for functional maturation of milk-secreting mammary epithelial cells. PERK-dependent signaling contributes to lipogenic differentiation in mammary epithelium, and perk deletion inhibits the sustained expression of lipogenic enzymes FAS, ACL, and SCD1. As a result, mammary tissue has reduced lipid content and the milk produced has altered lipid composition, resulting in attenuated pup growth. Consistent with PERK-dependent regulation of the lipogenic pathway, loss of PERK inhibits expression of FAS, ACL, and SCD1 in immortalized murine embryonic fibroblasts when cultured under conditions favoring adipocyte differentiation. These findings implicate PERK as a physiologically relevant regulator of the lipogenic pathway.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0808517105</identifier><identifier>PMID: 18852460</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Adipocytes ; Adipocytes - cytology ; Adipocytes - enzymology ; Animals ; Beta cells ; Biological Sciences ; Cell Differentiation ; Cells ; Cells, Cultured ; eIF-2 Kinase - genetics ; eIF-2 Kinase - metabolism ; eIF-2 Kinase - secretion ; Endoplasmic Reticulum - enzymology ; Enzyme Activation ; Enzymes ; Epithelial cells ; Epithelium - enzymology ; Epithelium - secretion ; Eukaryotic Initiation Factor-2 - metabolism ; Fatty acids ; Fibroblasts ; Gene Deletion ; Gene expression regulation ; Gene Expression Regulation, Enzymologic ; Kinases ; Lactation ; Lipids ; Lipogenesis ; Mammary glands ; Mammary Glands, Animal - cytology ; Mammary Glands, Animal - enzymology ; Membrane Proteins - metabolism ; Mice ; Milk ; Rodents ; Signal transduction ; Transcriptional regulatory elements</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2008-10, Vol.105 (42), p.16314-16319</ispartof><rights>Copyright 2008 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Oct 21, 2008</rights><rights>2008 by The National Academy of Sciences of the USA</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c589t-77ce4c390a0f739a6500f9314dddac34f8787dfe980b9dc18dca4009b28d0ccb3</citedby><cites>FETCH-LOGICAL-c589t-77ce4c390a0f739a6500f9314dddac34f8787dfe980b9dc18dca4009b28d0ccb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/105/42.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25465088$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25465088$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18852460$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bobrovnikova-Marjon, Ekaterina</creatorcontrib><creatorcontrib>Hatzivassiliou, Georgia</creatorcontrib><creatorcontrib>Grigoriadou, Christina</creatorcontrib><creatorcontrib>Romero, Margarita</creatorcontrib><creatorcontrib>Cavener, Douglas R</creatorcontrib><creatorcontrib>Thompson, Craig B</creatorcontrib><creatorcontrib>Diehl, J. Alan</creatorcontrib><title>PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The role of the endoplasmic reticulum stress-regulated kinase, PERK, in mammary gland function was assessed through generation of a targeted deletion in mammary epithelium. Characterization revealed that PERK is required for functional maturation of milk-secreting mammary epithelial cells. PERK-dependent signaling contributes to lipogenic differentiation in mammary epithelium, and perk deletion inhibits the sustained expression of lipogenic enzymes FAS, ACL, and SCD1. As a result, mammary tissue has reduced lipid content and the milk produced has altered lipid composition, resulting in attenuated pup growth. Consistent with PERK-dependent regulation of the lipogenic pathway, loss of PERK inhibits expression of FAS, ACL, and SCD1 in immortalized murine embryonic fibroblasts when cultured under conditions favoring adipocyte differentiation. These findings implicate PERK as a physiologically relevant regulator of the lipogenic pathway.</description><subject>Adipocytes</subject><subject>Adipocytes - cytology</subject><subject>Adipocytes - enzymology</subject><subject>Animals</subject><subject>Beta cells</subject><subject>Biological Sciences</subject><subject>Cell Differentiation</subject><subject>Cells</subject><subject>Cells, Cultured</subject><subject>eIF-2 Kinase - genetics</subject><subject>eIF-2 Kinase - metabolism</subject><subject>eIF-2 Kinase - secretion</subject><subject>Endoplasmic Reticulum - enzymology</subject><subject>Enzyme Activation</subject><subject>Enzymes</subject><subject>Epithelial cells</subject><subject>Epithelium - enzymology</subject><subject>Epithelium - secretion</subject><subject>Eukaryotic Initiation Factor-2 - metabolism</subject><subject>Fatty acids</subject><subject>Fibroblasts</subject><subject>Gene Deletion</subject><subject>Gene expression regulation</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Kinases</subject><subject>Lactation</subject><subject>Lipids</subject><subject>Lipogenesis</subject><subject>Mammary glands</subject><subject>Mammary Glands, Animal - cytology</subject><subject>Mammary Glands, Animal - enzymology</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Milk</subject><subject>Rodents</subject><subject>Signal transduction</subject><subject>Transcriptional regulatory elements</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1v1DAQxS0EoqVw5gRYHJA4pB3HdmJfkFBVPkQlENCz5fVH8CqJUzup6H-Pw666wIWTNZ7fPM2bh9BTAqcEWno2jTqfggDBSUuA30PHBCSpGibhPjoGqNtKsJodoUc5bwFAcgEP0RERgtesgWM0fLn4-qmybnKjdeOMk-uWXs8hjjh63Icpdm50OWRslxTGDg9xyQ4Pehh0usVdr0eLrbtxfZyGVWCttS1z5nZ22AbvXSr_4bfmY_TA6z67J_v3BF29u_h-_qG6_Pz-4_nby8pwIeeqbY1jhkrQ4FsqdcMBvKSEWWu1ocyLVrTWOylgI60hwhrNirlNLSwYs6En6M1Od1o2g7OmLJB0r6YU1q1V1EH93RnDD9XFG1XzFqTkReDVXiDF68XlWQ0hG9cXu64cQDWykRIkLeDLf8BtXNJYzKkaCBWMy7pAZzvIpJhzcv5uEwJqzVGtOapDjmXi-Z8GDvw-uALgPbBOHuS4YrUiTblVQV7_B1F-6fvZ_ZwL-2zHbvMc0x1cc1ZuL0Tpv9j1vY5KdylkdfVtNQiEt41glP4Ctw7IAA</recordid><startdate>20081021</startdate><enddate>20081021</enddate><creator>Bobrovnikova-Marjon, Ekaterina</creator><creator>Hatzivassiliou, Georgia</creator><creator>Grigoriadou, Christina</creator><creator>Romero, Margarita</creator><creator>Cavener, Douglas R</creator><creator>Thompson, Craig B</creator><creator>Diehl, J. Alan</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20081021</creationdate><title>PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation</title><author>Bobrovnikova-Marjon, Ekaterina ; Hatzivassiliou, Georgia ; Grigoriadou, Christina ; Romero, Margarita ; Cavener, Douglas R ; Thompson, Craig B ; Diehl, J. Alan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c589t-77ce4c390a0f739a6500f9314dddac34f8787dfe980b9dc18dca4009b28d0ccb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adipocytes</topic><topic>Adipocytes - cytology</topic><topic>Adipocytes - enzymology</topic><topic>Animals</topic><topic>Beta cells</topic><topic>Biological Sciences</topic><topic>Cell Differentiation</topic><topic>Cells</topic><topic>Cells, Cultured</topic><topic>eIF-2 Kinase - genetics</topic><topic>eIF-2 Kinase - metabolism</topic><topic>eIF-2 Kinase - secretion</topic><topic>Endoplasmic Reticulum - enzymology</topic><topic>Enzyme Activation</topic><topic>Enzymes</topic><topic>Epithelial cells</topic><topic>Epithelium - enzymology</topic><topic>Epithelium - secretion</topic><topic>Eukaryotic Initiation Factor-2 - metabolism</topic><topic>Fatty acids</topic><topic>Fibroblasts</topic><topic>Gene Deletion</topic><topic>Gene expression regulation</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Kinases</topic><topic>Lactation</topic><topic>Lipids</topic><topic>Lipogenesis</topic><topic>Mammary glands</topic><topic>Mammary Glands, Animal - cytology</topic><topic>Mammary Glands, Animal - enzymology</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice</topic><topic>Milk</topic><topic>Rodents</topic><topic>Signal transduction</topic><topic>Transcriptional regulatory elements</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bobrovnikova-Marjon, Ekaterina</creatorcontrib><creatorcontrib>Hatzivassiliou, Georgia</creatorcontrib><creatorcontrib>Grigoriadou, Christina</creatorcontrib><creatorcontrib>Romero, Margarita</creatorcontrib><creatorcontrib>Cavener, Douglas R</creatorcontrib><creatorcontrib>Thompson, Craig B</creatorcontrib><creatorcontrib>Diehl, J. Alan</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bobrovnikova-Marjon, Ekaterina</au><au>Hatzivassiliou, Georgia</au><au>Grigoriadou, Christina</au><au>Romero, Margarita</au><au>Cavener, Douglas R</au><au>Thompson, Craig B</au><au>Diehl, J. Alan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2008-10-21</date><risdate>2008</risdate><volume>105</volume><issue>42</issue><spage>16314</spage><epage>16319</epage><pages>16314-16319</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>The role of the endoplasmic reticulum stress-regulated kinase, PERK, in mammary gland function was assessed through generation of a targeted deletion in mammary epithelium. Characterization revealed that PERK is required for functional maturation of milk-secreting mammary epithelial cells. PERK-dependent signaling contributes to lipogenic differentiation in mammary epithelium, and perk deletion inhibits the sustained expression of lipogenic enzymes FAS, ACL, and SCD1. As a result, mammary tissue has reduced lipid content and the milk produced has altered lipid composition, resulting in attenuated pup growth. Consistent with PERK-dependent regulation of the lipogenic pathway, loss of PERK inhibits expression of FAS, ACL, and SCD1 in immortalized murine embryonic fibroblasts when cultured under conditions favoring adipocyte differentiation. These findings implicate PERK as a physiologically relevant regulator of the lipogenic pathway.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>18852460</pmid><doi>10.1073/pnas.0808517105</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2008-10, Vol.105 (42), p.16314-16319 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_crossref_primary_10_1073_pnas_0808517105 |
| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Adipocytes Adipocytes - cytology Adipocytes - enzymology Animals Beta cells Biological Sciences Cell Differentiation Cells Cells, Cultured eIF-2 Kinase - genetics eIF-2 Kinase - metabolism eIF-2 Kinase - secretion Endoplasmic Reticulum - enzymology Enzyme Activation Enzymes Epithelial cells Epithelium - enzymology Epithelium - secretion Eukaryotic Initiation Factor-2 - metabolism Fatty acids Fibroblasts Gene Deletion Gene expression regulation Gene Expression Regulation, Enzymologic Kinases Lactation Lipids Lipogenesis Mammary glands Mammary Glands, Animal - cytology Mammary Glands, Animal - enzymology Membrane Proteins - metabolism Mice Milk Rodents Signal transduction Transcriptional regulatory elements |
| title | PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T02%3A25%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=PERK-dependent%20regulation%20of%20lipogenesis%20during%20mouse%20mammary%20gland%20development%20and%20adipocyte%20differentiation&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Bobrovnikova-Marjon,%20Ekaterina&rft.date=2008-10-21&rft.volume=105&rft.issue=42&rft.spage=16314&rft.epage=16319&rft.pages=16314-16319&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.0808517105&rft_dat=%3Cjstor_cross%3E25465088%3C/jstor_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=201384592&rft_id=info:pmid/18852460&rft_jstor_id=25465088&rfr_iscdi=true |