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p53-independent functions of the p19(ARF) tumor suppressor
The p19(ARF) tumor suppressor antagonizes Mdm2 to induce p53-dependent cell cycle arrest. Individual TKO (triple knock out) mice nullizygous for ARF, p53, and Mdm2 develop multiple tumors at a frequency greater than those observed in animals lacking both p53 and Mdm2 or p53 alone, demonstrating that...
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| Published in: | Genes & development 2000-09, Vol.14 (18), p.2358-2365 |
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| Main Authors: | , , , , , , , |
| Format: | Article |
| Language: | English |
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| container_end_page | 2365 |
| container_issue | 18 |
| container_start_page | 2358 |
| container_title | Genes & development |
| container_volume | 14 |
| creator | Weber, J D Jeffers, J R Rehg, J E Randle, D H Lozano, G Roussel, M F Sherr, C J Zambetti, G P |
| description | The p19(ARF) tumor suppressor antagonizes Mdm2 to induce p53-dependent cell cycle arrest. Individual TKO (triple knock out) mice nullizygous for ARF, p53, and Mdm2 develop multiple tumors at a frequency greater than those observed in animals lacking both p53 and Mdm2 or p53 alone, demonstrating that p19(ARF) can act independently of the Mdm2-p53 axis in tumor surveillance. Reintroduction of ARF into TKO mouse embryo fibroblasts (MEFs), but not into those lacking both p53 and ARF, arrested the cell division cycle in the G1 phase. Inhibition of the retinoblastoma protein had no effect on the ability of ARF to arrest TKO MEFs. Thus, in the absence of Mdm2, p19(ARF) interacts with other targets to inhibit cell proliferation. |
| doi_str_mv | 10.1101/gad.827300 |
| format | article |
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Individual TKO (triple knock out) mice nullizygous for ARF, p53, and Mdm2 develop multiple tumors at a frequency greater than those observed in animals lacking both p53 and Mdm2 or p53 alone, demonstrating that p19(ARF) can act independently of the Mdm2-p53 axis in tumor surveillance. Reintroduction of ARF into TKO mouse embryo fibroblasts (MEFs), but not into those lacking both p53 and ARF, arrested the cell division cycle in the G1 phase. Inhibition of the retinoblastoma protein had no effect on the ability of ARF to arrest TKO MEFs. Thus, in the absence of Mdm2, p19(ARF) interacts with other targets to inhibit cell proliferation.</description><identifier>ISSN: 0890-9369</identifier><identifier>DOI: 10.1101/gad.827300</identifier><identifier>PMID: 10995391</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Cells, Cultured ; Fluorescent Antibody Technique ; Genes, Tumor Suppressor ; Immunoblotting ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neoplasms - genetics ; Neoplasms - pathology ; Nuclear Proteins ; Polymerase Chain Reaction ; Proteins - genetics ; Proteins - metabolism ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins - physiology ; Proto-Oncogene Proteins c-mdm2 ; Tumor Suppressor Protein p14ARF ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - physiology</subject><ispartof>Genes & development, 2000-09, Vol.14 (18), p.2358-2365</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10995391$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Weber, J D</creatorcontrib><creatorcontrib>Jeffers, J R</creatorcontrib><creatorcontrib>Rehg, J E</creatorcontrib><creatorcontrib>Randle, D H</creatorcontrib><creatorcontrib>Lozano, G</creatorcontrib><creatorcontrib>Roussel, M F</creatorcontrib><creatorcontrib>Sherr, C J</creatorcontrib><creatorcontrib>Zambetti, G P</creatorcontrib><title>p53-independent functions of the p19(ARF) tumor suppressor</title><title>Genes & development</title><addtitle>Genes Dev</addtitle><description>The p19(ARF) tumor suppressor antagonizes Mdm2 to induce p53-dependent cell cycle arrest. Individual TKO (triple knock out) mice nullizygous for ARF, p53, and Mdm2 develop multiple tumors at a frequency greater than those observed in animals lacking both p53 and Mdm2 or p53 alone, demonstrating that p19(ARF) can act independently of the Mdm2-p53 axis in tumor surveillance. Reintroduction of ARF into TKO mouse embryo fibroblasts (MEFs), but not into those lacking both p53 and ARF, arrested the cell division cycle in the G1 phase. Inhibition of the retinoblastoma protein had no effect on the ability of ARF to arrest TKO MEFs. Thus, in the absence of Mdm2, p19(ARF) interacts with other targets to inhibit cell proliferation.</description><subject>Animals</subject><subject>Cells, Cultured</subject><subject>Fluorescent Antibody Technique</subject><subject>Genes, Tumor Suppressor</subject><subject>Immunoblotting</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - pathology</subject><subject>Nuclear Proteins</subject><subject>Polymerase Chain Reaction</subject><subject>Proteins - genetics</subject><subject>Proteins - metabolism</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins - physiology</subject><subject>Proto-Oncogene Proteins c-mdm2</subject><subject>Tumor Suppressor Protein p14ARF</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - physiology</subject><issn>0890-9369</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><recordid>eNo1j81KxDAYRbNQnHF04wNIVqKLjl-StkncDYOjwoAgui75q1baJjbJwrefguPmHi4cLlyErgisCQFy_6nsWlDOAE7QEoSEQrJaLtB5jN8AUENdn6EFASkrJskSPYSKFd1oXXBzjAm3eTSp82PEvsXpy-FA5O3mbXeHUx78hGMOYXIx-ukCnbaqj-7yyBX62D2-b5-L_evTy3azLwIFngplmSmrVghaaeBlZbgSvFac2xJabSoDc5MOtDNGUUGIoFpDyUtFbatAshW6-dsNk__JLqZm6KJxfa9G53NsOKUcQNJZvD6KWQ_ONmHqBjX9Nv9v2QFKc1LW</recordid><startdate>20000915</startdate><enddate>20000915</enddate><creator>Weber, J D</creator><creator>Jeffers, J R</creator><creator>Rehg, J E</creator><creator>Randle, D H</creator><creator>Lozano, G</creator><creator>Roussel, M F</creator><creator>Sherr, C J</creator><creator>Zambetti, G P</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>20000915</creationdate><title>p53-independent functions of the p19(ARF) tumor suppressor</title><author>Weber, J D ; Jeffers, J R ; Rehg, J E ; Randle, D H ; Lozano, G ; Roussel, M F ; Sherr, C J ; Zambetti, G P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p207t-ad3c45f8825b0745c7a876a77d40fbc5c076a9e0becca281182bb0474a2dfa093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Cells, Cultured</topic><topic>Fluorescent Antibody Technique</topic><topic>Genes, Tumor Suppressor</topic><topic>Immunoblotting</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - pathology</topic><topic>Nuclear Proteins</topic><topic>Polymerase Chain Reaction</topic><topic>Proteins - genetics</topic><topic>Proteins - metabolism</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins - physiology</topic><topic>Proto-Oncogene Proteins c-mdm2</topic><topic>Tumor Suppressor Protein p14ARF</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Weber, J D</creatorcontrib><creatorcontrib>Jeffers, J R</creatorcontrib><creatorcontrib>Rehg, J E</creatorcontrib><creatorcontrib>Randle, D H</creatorcontrib><creatorcontrib>Lozano, G</creatorcontrib><creatorcontrib>Roussel, M F</creatorcontrib><creatorcontrib>Sherr, C J</creatorcontrib><creatorcontrib>Zambetti, G P</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>Weber, J D</au><au>Jeffers, J R</au><au>Rehg, J E</au><au>Randle, D H</au><au>Lozano, G</au><au>Roussel, M F</au><au>Sherr, C J</au><au>Zambetti, G P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>p53-independent functions of the p19(ARF) tumor suppressor</atitle><jtitle>Genes & development</jtitle><addtitle>Genes Dev</addtitle><date>2000-09-15</date><risdate>2000</risdate><volume>14</volume><issue>18</issue><spage>2358</spage><epage>2365</epage><pages>2358-2365</pages><issn>0890-9369</issn><abstract>The p19(ARF) tumor suppressor antagonizes Mdm2 to induce p53-dependent cell cycle arrest. 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| identifier | ISSN: 0890-9369 |
| ispartof | Genes & development, 2000-09, Vol.14 (18), p.2358-2365 |
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| language | eng |
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| source | Open Access: PubMed Central; Freely Accessible Science Journals - check A-Z of ejournals |
| subjects | Animals Cells, Cultured Fluorescent Antibody Technique Genes, Tumor Suppressor Immunoblotting Mice Mice, Inbred C57BL Mice, Knockout Neoplasms - genetics Neoplasms - pathology Nuclear Proteins Polymerase Chain Reaction Proteins - genetics Proteins - metabolism Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - physiology Proto-Oncogene Proteins c-mdm2 Tumor Suppressor Protein p14ARF Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - physiology |
| title | p53-independent functions of the p19(ARF) tumor suppressor |
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