Delta40p53 controls the switch from pluripotency to differentiation by regulating IGF signaling in ESCs
Δ40p53 is a transactivation-deficient isoform of the tumor suppressor p53. We discovered that Δ40p53, in addition to being highly expressed in embryonic stem cells (ESCs), is the major p53 isoform during early stages of embryogenesis in the mouse. By altering the dose of Δ40p53 in ESCs, we identifie...
Gespeichert in:
| Veröffentlicht in: | Genes & development 2010-11, Vol.24 (21), p.2408-2419 |
|---|---|
| Hauptverfasser: | , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2419 |
|---|---|
| container_issue | 21 |
| container_start_page | 2408 |
| container_title | Genes & development |
| container_volume | 24 |
| creator | Ungewitter, Erica Scrable, Heidi |
| description | Δ40p53 is a transactivation-deficient isoform of the tumor suppressor p53. We discovered that Δ40p53, in addition to being highly expressed in embryonic stem cells (ESCs), is the major p53 isoform during early stages of embryogenesis in the mouse. By altering the dose of Δ40p53 in ESCs, we identified a critical role for this isoform in maintaining the ESC state. Haploinsufficiency for Δ40p53 causes a loss of pluripotency in ESCs and acquisition of a somatic cell cycle, while increased dosage of Δ40p53 prolongs pluripotency and inhibits progression to a more differentiated state. Δ40p53 controls the switch from pluripotent ESCs to differentiated somatic cells by controlling the activity of full-length p53 at critical targets such as Nanog and the IGF-1 receptor (IGF-1R). The IGF axis plays a central role in the switch between pluripotency and differentiation in ESCs-and Δ40p53, by controlling the level of the IGF-1R, acts as a master regulator of this switch. We propose that this is the primary function of Δ40p53 in cells of the early embryo and stem cells, which are the only normal cells in which this isoform is expressed. |
| doi_str_mv | 10.1101/gad.1987810 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_762284439</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>762284439</sourcerecordid><originalsourceid>FETCH-LOGICAL-p559-edcb1d8d7d046f296c67a2df236cd45b4fb917f97c9c83380a464f641e60622e3</originalsourceid><addsrcrecordid>eNo1kM9LwzAAhYMgbk5P3iU3T51JmybNUeY2BwMP7l7S_OgiWVKTFNl_b8V5enzw8eA9AB4wWmKM8HMv1BLzhjUYXYE5rgkvasLYDNym9IkQoojSGzArMSKYID4H_at2WRA01BWUwecYXIL5qGH6tlkeoYnhBAc3RjuErL08wxygssboqH22ItvgYXeGUfejm8j3cLfdwGR7L9wvWQ_XH6t0B66NcEnfX3IBDpv1YfVW7N-3u9XLvhjqmhdayQ6rRjGFCDUlp5IyUSpTVlQqUnfEdBwzw5nksqmqBglCiaEE62lYWepqAZ7-aocYvkadcnuySWrnhNdhTC2brIaQik_m48Ucu5NW7RDtScRz-39N9QOn32Oi</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>762284439</pqid></control><display><type>article</type><title>Delta40p53 controls the switch from pluripotency to differentiation by regulating IGF signaling in ESCs</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Ungewitter, Erica ; Scrable, Heidi</creator><creatorcontrib>Ungewitter, Erica ; Scrable, Heidi</creatorcontrib><description>Δ40p53 is a transactivation-deficient isoform of the tumor suppressor p53. We discovered that Δ40p53, in addition to being highly expressed in embryonic stem cells (ESCs), is the major p53 isoform during early stages of embryogenesis in the mouse. By altering the dose of Δ40p53 in ESCs, we identified a critical role for this isoform in maintaining the ESC state. Haploinsufficiency for Δ40p53 causes a loss of pluripotency in ESCs and acquisition of a somatic cell cycle, while increased dosage of Δ40p53 prolongs pluripotency and inhibits progression to a more differentiated state. Δ40p53 controls the switch from pluripotent ESCs to differentiated somatic cells by controlling the activity of full-length p53 at critical targets such as Nanog and the IGF-1 receptor (IGF-1R). The IGF axis plays a central role in the switch between pluripotency and differentiation in ESCs-and Δ40p53, by controlling the level of the IGF-1R, acts as a master regulator of this switch. We propose that this is the primary function of Δ40p53 in cells of the early embryo and stem cells, which are the only normal cells in which this isoform is expressed.</description><identifier>EISSN: 1549-5477</identifier><identifier>DOI: 10.1101/gad.1987810</identifier><identifier>PMID: 21041409</identifier><language>eng</language><publisher>United States</publisher><subject>Amino Acid Sequence ; Animals ; Blotting, Western ; Cell Cycle ; Cell Differentiation ; Cell Line ; Cell Nucleus - metabolism ; Cell Survival ; Cytoplasm - metabolism ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - metabolism ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Humans ; Immunohistochemistry ; Mice ; Mice, 129 Strain ; Mice, Inbred ICR ; Molecular Sequence Data ; Nanog Homeobox Protein ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphorylation ; Pluripotent Stem Cells - cytology ; Pluripotent Stem Cells - metabolism ; Protein Isoforms - genetics ; Protein Isoforms - metabolism ; Protein Isoforms - physiology ; Receptor, IGF Type 1 - genetics ; Receptor, IGF Type 1 - physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; Tumor Suppressor Protein p53 - physiology</subject><ispartof>Genes & development, 2010-11, Vol.24 (21), p.2408-2419</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21041409$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ungewitter, Erica</creatorcontrib><creatorcontrib>Scrable, Heidi</creatorcontrib><title>Delta40p53 controls the switch from pluripotency to differentiation by regulating IGF signaling in ESCs</title><title>Genes & development</title><addtitle>Genes Dev</addtitle><description>Δ40p53 is a transactivation-deficient isoform of the tumor suppressor p53. We discovered that Δ40p53, in addition to being highly expressed in embryonic stem cells (ESCs), is the major p53 isoform during early stages of embryogenesis in the mouse. By altering the dose of Δ40p53 in ESCs, we identified a critical role for this isoform in maintaining the ESC state. Haploinsufficiency for Δ40p53 causes a loss of pluripotency in ESCs and acquisition of a somatic cell cycle, while increased dosage of Δ40p53 prolongs pluripotency and inhibits progression to a more differentiated state. Δ40p53 controls the switch from pluripotent ESCs to differentiated somatic cells by controlling the activity of full-length p53 at critical targets such as Nanog and the IGF-1 receptor (IGF-1R). The IGF axis plays a central role in the switch between pluripotency and differentiation in ESCs-and Δ40p53, by controlling the level of the IGF-1R, acts as a master regulator of this switch. We propose that this is the primary function of Δ40p53 in cells of the early embryo and stem cells, which are the only normal cells in which this isoform is expressed.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cell Cycle</subject><subject>Cell Differentiation</subject><subject>Cell Line</subject><subject>Cell Nucleus - metabolism</subject><subject>Cell Survival</subject><subject>Cytoplasm - metabolism</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Mice</subject><subject>Mice, 129 Strain</subject><subject>Mice, Inbred ICR</subject><subject>Molecular Sequence Data</subject><subject>Nanog Homeobox Protein</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphorylation</subject><subject>Pluripotent Stem Cells - cytology</subject><subject>Pluripotent Stem Cells - metabolism</subject><subject>Protein Isoforms - genetics</subject><subject>Protein Isoforms - metabolism</subject><subject>Protein Isoforms - physiology</subject><subject>Receptor, IGF Type 1 - genetics</subject><subject>Receptor, IGF Type 1 - physiology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Signal Transduction</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tumor Suppressor Protein p53 - physiology</subject><issn>1549-5477</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kM9LwzAAhYMgbk5P3iU3T51JmybNUeY2BwMP7l7S_OgiWVKTFNl_b8V5enzw8eA9AB4wWmKM8HMv1BLzhjUYXYE5rgkvasLYDNym9IkQoojSGzArMSKYID4H_at2WRA01BWUwecYXIL5qGH6tlkeoYnhBAc3RjuErL08wxygssboqH22ItvgYXeGUfejm8j3cLfdwGR7L9wvWQ_XH6t0B66NcEnfX3IBDpv1YfVW7N-3u9XLvhjqmhdayQ6rRjGFCDUlp5IyUSpTVlQqUnfEdBwzw5nksqmqBglCiaEE62lYWepqAZ7-aocYvkadcnuySWrnhNdhTC2brIaQik_m48Ucu5NW7RDtScRz-39N9QOn32Oi</recordid><startdate>20101101</startdate><enddate>20101101</enddate><creator>Ungewitter, Erica</creator><creator>Scrable, Heidi</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20101101</creationdate><title>Delta40p53 controls the switch from pluripotency to differentiation by regulating IGF signaling in ESCs</title><author>Ungewitter, Erica ; Scrable, Heidi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p559-edcb1d8d7d046f296c67a2df236cd45b4fb917f97c9c83380a464f641e60622e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Blotting, Western</topic><topic>Cell Cycle</topic><topic>Cell Differentiation</topic><topic>Cell Line</topic><topic>Cell Nucleus - metabolism</topic><topic>Cell Survival</topic><topic>Cytoplasm - metabolism</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Mice</topic><topic>Mice, 129 Strain</topic><topic>Mice, Inbred ICR</topic><topic>Molecular Sequence Data</topic><topic>Nanog Homeobox Protein</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Phosphorylation</topic><topic>Pluripotent Stem Cells - cytology</topic><topic>Pluripotent Stem Cells - metabolism</topic><topic>Protein Isoforms - genetics</topic><topic>Protein Isoforms - metabolism</topic><topic>Protein Isoforms - physiology</topic><topic>Receptor, IGF Type 1 - genetics</topic><topic>Receptor, IGF Type 1 - physiology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Signal Transduction</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Tumor Suppressor Protein p53 - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ungewitter, Erica</creatorcontrib><creatorcontrib>Scrable, Heidi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Genes & development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ungewitter, Erica</au><au>Scrable, Heidi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Delta40p53 controls the switch from pluripotency to differentiation by regulating IGF signaling in ESCs</atitle><jtitle>Genes & development</jtitle><addtitle>Genes Dev</addtitle><date>2010-11-01</date><risdate>2010</risdate><volume>24</volume><issue>21</issue><spage>2408</spage><epage>2419</epage><pages>2408-2419</pages><eissn>1549-5477</eissn><abstract>Δ40p53 is a transactivation-deficient isoform of the tumor suppressor p53. We discovered that Δ40p53, in addition to being highly expressed in embryonic stem cells (ESCs), is the major p53 isoform during early stages of embryogenesis in the mouse. By altering the dose of Δ40p53 in ESCs, we identified a critical role for this isoform in maintaining the ESC state. Haploinsufficiency for Δ40p53 causes a loss of pluripotency in ESCs and acquisition of a somatic cell cycle, while increased dosage of Δ40p53 prolongs pluripotency and inhibits progression to a more differentiated state. Δ40p53 controls the switch from pluripotent ESCs to differentiated somatic cells by controlling the activity of full-length p53 at critical targets such as Nanog and the IGF-1 receptor (IGF-1R). The IGF axis plays a central role in the switch between pluripotency and differentiation in ESCs-and Δ40p53, by controlling the level of the IGF-1R, acts as a master regulator of this switch. We propose that this is the primary function of Δ40p53 in cells of the early embryo and stem cells, which are the only normal cells in which this isoform is expressed.</abstract><cop>United States</cop><pmid>21041409</pmid><doi>10.1101/gad.1987810</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | EISSN: 1549-5477 |
| ispartof | Genes & development, 2010-11, Vol.24 (21), p.2408-2419 |
| issn | 1549-5477 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_762284439 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Amino Acid Sequence Animals Blotting, Western Cell Cycle Cell Differentiation Cell Line Cell Nucleus - metabolism Cell Survival Cytoplasm - metabolism Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humans Immunohistochemistry Mice Mice, 129 Strain Mice, Inbred ICR Molecular Sequence Data Nanog Homeobox Protein Phosphatidylinositol 3-Kinases - metabolism Phosphorylation Pluripotent Stem Cells - cytology Pluripotent Stem Cells - metabolism Protein Isoforms - genetics Protein Isoforms - metabolism Protein Isoforms - physiology Receptor, IGF Type 1 - genetics Receptor, IGF Type 1 - physiology Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Tumor Suppressor Protein p53 - physiology |
| title | Delta40p53 controls the switch from pluripotency to differentiation by regulating IGF signaling in ESCs |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-30T11%3A33%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Delta40p53%20controls%20the%20switch%20from%20pluripotency%20to%20differentiation%20by%20regulating%20IGF%20signaling%20in%20ESCs&rft.jtitle=Genes%20&%20development&rft.au=Ungewitter,%20Erica&rft.date=2010-11-01&rft.volume=24&rft.issue=21&rft.spage=2408&rft.epage=2419&rft.pages=2408-2419&rft.eissn=1549-5477&rft_id=info:doi/10.1101/gad.1987810&rft_dat=%3Cproquest_pubme%3E762284439%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=762284439&rft_id=info:pmid/21041409&rfr_iscdi=true |