PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms
We show in this study that PTEN regulates p53 protein levels and transcriptional activity through both phosphatase-dependent and -independent mechanisms. The onset of tumor development in p53 +/−; Pten +/− mice is similar to p53 −/− animals, and p53 protein levels are dramatically reduced in Pten −/...
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| Veröffentlicht in: | Cancer cell 2003-02, Vol.3 (2), p.117-130 |
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| creator | Freeman, Daniel J. Li, Andrew G. Wei, Gang Li, Heng-Hong Kertesz, Nathalie Lesche, Ralf Whale, Andrew D. Martinez-Diaz, Hilda Rozengurt, Nora Cardiff, Robert D. Liu, Xuan Wu, Hong |
| description | We show in this study that PTEN regulates p53 protein levels and transcriptional activity through both phosphatase-dependent and -independent mechanisms. The onset of tumor development in
p53
+/−;
Pten
+/− mice is similar to
p53
−/− animals, and p53 protein levels are dramatically reduced in
Pten
−/−
cells and tissues. Reintroducing wild-type or phosphatase-dead PTEN mutants leads to a significant increase in p53 stability. PTEN also physically associates with endogenous p53. Finally, PTEN regulates the transcriptional activity of p53 by modulating its DNA binding activity. This study provides a novel mechanism by which the loss of PTEN can functionally control “two” hits in the course of tumor development by concurrently modulating p53 activity. |
| doi_str_mv | 10.1016/S1535-6108(03)00021-7 |
| format | Article |
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p53
+/−;
Pten
+/− mice is similar to
p53
−/− animals, and p53 protein levels are dramatically reduced in
Pten
−/−
cells and tissues. Reintroducing wild-type or phosphatase-dead PTEN mutants leads to a significant increase in p53 stability. PTEN also physically associates with endogenous p53. Finally, PTEN regulates the transcriptional activity of p53 by modulating its DNA binding activity. This study provides a novel mechanism by which the loss of PTEN can functionally control “two” hits in the course of tumor development by concurrently modulating p53 activity.</description><identifier>ISSN: 1535-6108</identifier><identifier>EISSN: 1878-3686</identifier><identifier>DOI: 10.1016/S1535-6108(03)00021-7</identifier><identifier>PMID: 12620407</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Blotting, Northern ; Blotting, Western ; Cell Line ; Chromatin - chemistry ; Chromatin - metabolism ; Cyclin D1 - metabolism ; Electrophoretic Mobility Shift Assay ; Fibroblasts - physiology ; Gene Expression Regulation ; Genes, Tumor Suppressor - physiology ; Glutathione Transferase - metabolism ; Humans ; Immunoblotting ; Mice ; Mice, Knockout ; Nuclear Proteins ; Phosphoric Monoester Hydrolases - metabolism ; Phosphoric Monoester Hydrolases - physiology ; Precipitin Tests ; Proto-Oncogene Proteins - metabolism ; Proto-Oncogene Proteins c-mdm2 ; PTEN Phosphohydrolase ; Transfection ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; Tumor Suppressor Proteins - physiology</subject><ispartof>Cancer cell, 2003-02, Vol.3 (2), p.117-130</ispartof><rights>2003 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-70f93f7cb5336cf1a86807a7582fd8020370adf1a7b8a7fdb510acfed8ffedbc3</citedby><cites>FETCH-LOGICAL-c491t-70f93f7cb5336cf1a86807a7582fd8020370adf1a7b8a7fdb510acfed8ffedbc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1535610803000217$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12620407$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Freeman, Daniel J.</creatorcontrib><creatorcontrib>Li, Andrew G.</creatorcontrib><creatorcontrib>Wei, Gang</creatorcontrib><creatorcontrib>Li, Heng-Hong</creatorcontrib><creatorcontrib>Kertesz, Nathalie</creatorcontrib><creatorcontrib>Lesche, Ralf</creatorcontrib><creatorcontrib>Whale, Andrew D.</creatorcontrib><creatorcontrib>Martinez-Diaz, Hilda</creatorcontrib><creatorcontrib>Rozengurt, Nora</creatorcontrib><creatorcontrib>Cardiff, Robert D.</creatorcontrib><creatorcontrib>Liu, Xuan</creatorcontrib><creatorcontrib>Wu, Hong</creatorcontrib><title>PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms</title><title>Cancer cell</title><addtitle>Cancer Cell</addtitle><description>We show in this study that PTEN regulates p53 protein levels and transcriptional activity through both phosphatase-dependent and -independent mechanisms. The onset of tumor development in
p53
+/−;
Pten
+/− mice is similar to
p53
−/− animals, and p53 protein levels are dramatically reduced in
Pten
−/−
cells and tissues. Reintroducing wild-type or phosphatase-dead PTEN mutants leads to a significant increase in p53 stability. PTEN also physically associates with endogenous p53. Finally, PTEN regulates the transcriptional activity of p53 by modulating its DNA binding activity. This study provides a novel mechanism by which the loss of PTEN can functionally control “two” hits in the course of tumor development by concurrently modulating p53 activity.</description><subject>Animals</subject><subject>Blotting, Northern</subject><subject>Blotting, Western</subject><subject>Cell Line</subject><subject>Chromatin - chemistry</subject><subject>Chromatin - metabolism</subject><subject>Cyclin D1 - metabolism</subject><subject>Electrophoretic Mobility Shift Assay</subject><subject>Fibroblasts - physiology</subject><subject>Gene Expression Regulation</subject><subject>Genes, Tumor Suppressor - physiology</subject><subject>Glutathione Transferase - metabolism</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Nuclear Proteins</subject><subject>Phosphoric Monoester Hydrolases - metabolism</subject><subject>Phosphoric Monoester Hydrolases - physiology</subject><subject>Precipitin Tests</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Proto-Oncogene Proteins c-mdm2</subject><subject>PTEN Phosphohydrolase</subject><subject>Transfection</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tumor Suppressor Proteins - physiology</subject><issn>1535-6108</issn><issn>1878-3686</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9v1DAQxS0Eou2WjwDKCcEhdBxvYu8JVVUpSBVFoj1bjj1ujPIPj7PSfnvc3UU99jIejX4zT36PsfccvnDgzcVvXou6bDioTyA-A0DFS_mKnXIlVSka1bzO_X_khJ0R_YG8x-XmLTvhVVPBGuQp2_26v_5ZpGWYYkHLPEckym3Ex6U3CamYa1HMcUoYxqLHLfZUmNEVxqawDWlXpC5Oy2NXzN1Ec2eSISwdzjg6HNMeLcP4PBjQdmYMNNA5e-NNT_ju-K7Yw7fr-6vv5e3dzY-ry9vSrjc8lRL8Rnhp21qIxnpuVKNAGlmryjsFFQgJxuW5bJWR3rU1B2M9OuVzaa1YsY-Hu_kXfxekpIdAFvvejDgtpKUAKRVXL4LZ2aaSYp3B-gDaOBFF9HqOYTBxpznop3D0Phz95LwGoffhZJ0V-3AUWNoB3fPWMY0MfD0A2WXcBoyabMDRogsRbdJuCi9I_AM39aG4</recordid><startdate>20030201</startdate><enddate>20030201</enddate><creator>Freeman, Daniel J.</creator><creator>Li, Andrew G.</creator><creator>Wei, Gang</creator><creator>Li, Heng-Hong</creator><creator>Kertesz, Nathalie</creator><creator>Lesche, Ralf</creator><creator>Whale, Andrew D.</creator><creator>Martinez-Diaz, Hilda</creator><creator>Rozengurt, Nora</creator><creator>Cardiff, Robert D.</creator><creator>Liu, Xuan</creator><creator>Wu, Hong</creator><general>Elsevier Inc</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>7TO</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20030201</creationdate><title>PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms</title><author>Freeman, Daniel J. ; Li, Andrew G. ; Wei, Gang ; Li, Heng-Hong ; Kertesz, Nathalie ; Lesche, Ralf ; Whale, Andrew D. ; Martinez-Diaz, Hilda ; Rozengurt, Nora ; Cardiff, Robert D. ; Liu, Xuan ; Wu, Hong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-70f93f7cb5336cf1a86807a7582fd8020370adf1a7b8a7fdb510acfed8ffedbc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Blotting, Northern</topic><topic>Blotting, Western</topic><topic>Cell Line</topic><topic>Chromatin - chemistry</topic><topic>Chromatin - metabolism</topic><topic>Cyclin D1 - metabolism</topic><topic>Electrophoretic Mobility Shift Assay</topic><topic>Fibroblasts - physiology</topic><topic>Gene Expression Regulation</topic><topic>Genes, Tumor Suppressor - physiology</topic><topic>Glutathione Transferase - metabolism</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Nuclear Proteins</topic><topic>Phosphoric Monoester Hydrolases - metabolism</topic><topic>Phosphoric Monoester Hydrolases - physiology</topic><topic>Precipitin Tests</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Proto-Oncogene Proteins c-mdm2</topic><topic>PTEN Phosphohydrolase</topic><topic>Transfection</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Tumor Suppressor Proteins - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Freeman, Daniel J.</creatorcontrib><creatorcontrib>Li, Andrew G.</creatorcontrib><creatorcontrib>Wei, Gang</creatorcontrib><creatorcontrib>Li, Heng-Hong</creatorcontrib><creatorcontrib>Kertesz, Nathalie</creatorcontrib><creatorcontrib>Lesche, Ralf</creatorcontrib><creatorcontrib>Whale, Andrew D.</creatorcontrib><creatorcontrib>Martinez-Diaz, Hilda</creatorcontrib><creatorcontrib>Rozengurt, Nora</creatorcontrib><creatorcontrib>Cardiff, Robert D.</creatorcontrib><creatorcontrib>Liu, Xuan</creatorcontrib><creatorcontrib>Wu, Hong</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>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Freeman, Daniel J.</au><au>Li, Andrew G.</au><au>Wei, Gang</au><au>Li, Heng-Hong</au><au>Kertesz, Nathalie</au><au>Lesche, Ralf</au><au>Whale, Andrew D.</au><au>Martinez-Diaz, Hilda</au><au>Rozengurt, Nora</au><au>Cardiff, Robert D.</au><au>Liu, Xuan</au><au>Wu, Hong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms</atitle><jtitle>Cancer cell</jtitle><addtitle>Cancer Cell</addtitle><date>2003-02-01</date><risdate>2003</risdate><volume>3</volume><issue>2</issue><spage>117</spage><epage>130</epage><pages>117-130</pages><issn>1535-6108</issn><eissn>1878-3686</eissn><abstract>We show in this study that PTEN regulates p53 protein levels and transcriptional activity through both phosphatase-dependent and -independent mechanisms. The onset of tumor development in
p53
+/−;
Pten
+/− mice is similar to
p53
−/− animals, and p53 protein levels are dramatically reduced in
Pten
−/−
cells and tissues. Reintroducing wild-type or phosphatase-dead PTEN mutants leads to a significant increase in p53 stability. PTEN also physically associates with endogenous p53. Finally, PTEN regulates the transcriptional activity of p53 by modulating its DNA binding activity. This study provides a novel mechanism by which the loss of PTEN can functionally control “two” hits in the course of tumor development by concurrently modulating p53 activity.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12620407</pmid><doi>10.1016/S1535-6108(03)00021-7</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Blotting, Northern Blotting, Western Cell Line Chromatin - chemistry Chromatin - metabolism Cyclin D1 - metabolism Electrophoretic Mobility Shift Assay Fibroblasts - physiology Gene Expression Regulation Genes, Tumor Suppressor - physiology Glutathione Transferase - metabolism Humans Immunoblotting Mice Mice, Knockout Nuclear Proteins Phosphoric Monoester Hydrolases - metabolism Phosphoric Monoester Hydrolases - physiology Precipitin Tests Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins c-mdm2 PTEN Phosphohydrolase Transfection Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Tumor Suppressor Proteins - physiology |
| title | PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms |
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