Impaired regulation of tumor suppressor p53 caused by mutations in the xeroderma pigmentosum DDB2 gene: mutual regulatory interactions between p48(DDB2) and p53
Tumor suppressor p53 controls cell cycle progression and apoptosis following DNA damage, thus minimizing carcinogenesis. Mutations in the human DDB2 gene generate the E subgroup of xeroderma pigmentosum (XP-E). We report here that XP-E strains are defective in UV irradiation-induced apoptosis due to...
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| Veröffentlicht in: | Molecular and cellular biology 2003-11, Vol.23 (21), p.7540 |
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| container_title | Molecular and cellular biology |
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| creator | Itoh, Toshiki O'Shea, Cristin Linn, Stuart |
| description | Tumor suppressor p53 controls cell cycle progression and apoptosis following DNA damage, thus minimizing carcinogenesis. Mutations in the human DDB2 gene generate the E subgroup of xeroderma pigmentosum (XP-E). We report here that XP-E strains are defective in UV irradiation-induced apoptosis due to severely reduced basal and UV-induced p53 levels. These defects are restored by infection with a p53 cDNA expression construct or with a DDB2 expression construct if and only if it contains intron 4, which includes a nonmutated p53 consensus-binding site. We propose that both before and after UV irradiation, DDB2 directly regulates p53 levels, while DDB2 expression is itself regulated by p53. |
| doi_str_mv | 10.1128/MCB.23.21.7540-7553.2003 |
| format | Article |
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Mutations in the human DDB2 gene generate the E subgroup of xeroderma pigmentosum (XP-E). We report here that XP-E strains are defective in UV irradiation-induced apoptosis due to severely reduced basal and UV-induced p53 levels. These defects are restored by infection with a p53 cDNA expression construct or with a DDB2 expression construct if and only if it contains intron 4, which includes a nonmutated p53 consensus-binding site. 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Mutations in the human DDB2 gene generate the E subgroup of xeroderma pigmentosum (XP-E). We report here that XP-E strains are defective in UV irradiation-induced apoptosis due to severely reduced basal and UV-induced p53 levels. These defects are restored by infection with a p53 cDNA expression construct or with a DDB2 expression construct if and only if it contains intron 4, which includes a nonmutated p53 consensus-binding site. We propose that both before and after UV irradiation, DDB2 directly regulates p53 levels, while DDB2 expression is itself regulated by p53.</description><subject>Apoptosis - physiology</subject><subject>Cell Line</subject><subject>DNA - metabolism</subject><subject>DNA - radiation effects</subject><subject>DNA Damage</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Genes, Tumor Suppressor</subject><subject>Humans</subject><subject>Introns</subject><subject>Mutation</subject><subject>Phenotype</subject><subject>Signal Transduction - physiology</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Ultraviolet Rays</subject><subject>Xeroderma Pigmentosum</subject><issn>0270-7306</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kM1OwzAQhH0A0VJ4BeQjHBL8n4QbbfmpVMQFzpVjb0tQnVi2I-jb8KiklJ52ZzXfjLQIYUpySll5-zKb5oznjOaFFCQrpBwEIfwEjQkrhgMnaoTOY_wkhKiK8DM0okKqQbEx-lk4r5sAFgfY9Fudmq7F3Rqn3nUBx977ADEOq5ccG93HwVnvsOvTnzXipsXpA_A3hM5CcBr7ZuOgTV3sHZ7PpwxvoIW7PdHr7bGlC7uBTBC0OcTUkL4AWuxFeb2nbrBu7b70Ap2u9TbC5f-coPfHh7fZc7Z8fVrM7peZZ6RImTKiFEYVikJdsVLUrDRlKaUSpQVmqTUMqDBVIUEVRHFWWcELaZgxlFSW8gm6OuT6vnZgVz40Tofd6vgq_gv6sGwe</recordid><startdate>200311</startdate><enddate>200311</enddate><creator>Itoh, Toshiki</creator><creator>O'Shea, Cristin</creator><creator>Linn, Stuart</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>200311</creationdate><title>Impaired regulation of tumor suppressor p53 caused by mutations in the xeroderma pigmentosum DDB2 gene: mutual regulatory interactions between p48(DDB2) and p53</title><author>Itoh, Toshiki ; O'Shea, Cristin ; Linn, Stuart</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p207t-6c484c6761eb9284b28c8855648de2d1dc2e14c975e6706329d4375c2cc109d13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Apoptosis - physiology</topic><topic>Cell Line</topic><topic>DNA - metabolism</topic><topic>DNA - radiation effects</topic><topic>DNA Damage</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Genes, Tumor Suppressor</topic><topic>Humans</topic><topic>Introns</topic><topic>Mutation</topic><topic>Phenotype</topic><topic>Signal Transduction - physiology</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Ultraviolet Rays</topic><topic>Xeroderma Pigmentosum</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Itoh, Toshiki</creatorcontrib><creatorcontrib>O'Shea, Cristin</creatorcontrib><creatorcontrib>Linn, Stuart</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Molecular and cellular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Itoh, Toshiki</au><au>O'Shea, Cristin</au><au>Linn, Stuart</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impaired regulation of tumor suppressor p53 caused by mutations in the xeroderma pigmentosum DDB2 gene: mutual regulatory interactions between p48(DDB2) and p53</atitle><jtitle>Molecular and cellular biology</jtitle><addtitle>Mol Cell Biol</addtitle><date>2003-11</date><risdate>2003</risdate><volume>23</volume><issue>21</issue><spage>7540</spage><pages>7540-</pages><issn>0270-7306</issn><abstract>Tumor suppressor p53 controls cell cycle progression and apoptosis following DNA damage, thus minimizing carcinogenesis. Mutations in the human DDB2 gene generate the E subgroup of xeroderma pigmentosum (XP-E). We report here that XP-E strains are defective in UV irradiation-induced apoptosis due to severely reduced basal and UV-induced p53 levels. These defects are restored by infection with a p53 cDNA expression construct or with a DDB2 expression construct if and only if it contains intron 4, which includes a nonmutated p53 consensus-binding site. We propose that both before and after UV irradiation, DDB2 directly regulates p53 levels, while DDB2 expression is itself regulated by p53.</abstract><cop>United States</cop><pmid>14560002</pmid><doi>10.1128/MCB.23.21.7540-7553.2003</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | Molecular and cellular biology, 2003-11, Vol.23 (21), p.7540 |
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| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Apoptosis - physiology Cell Line DNA - metabolism DNA - radiation effects DNA Damage DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Gene Expression Regulation Genes, Tumor Suppressor Humans Introns Mutation Phenotype Signal Transduction - physiology Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Ultraviolet Rays Xeroderma Pigmentosum |
| title | Impaired regulation of tumor suppressor p53 caused by mutations in the xeroderma pigmentosum DDB2 gene: mutual regulatory interactions between p48(DDB2) and p53 |
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