HOXA5-Twist Interaction Alters p53 Homeostasis in Breast Cancer Cells
The homeotic gene HOXA5 has been shown to play an important role in breast tumorigenesis. We have shown that loss of p53 correlated with loss of a developmentally regulated transcription factor, HOXA5, in primary breast cancer. Searching for potential protein interacting partners we found that HOXA5...
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| Veröffentlicht in: | The Journal of biological chemistry 2005-01, Vol.280 (3), p.2294-2299 |
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| container_title | The Journal of biological chemistry |
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| creator | Stasinopoulos, Ioannis A. Mironchik, Yelena Raman, Ana Wildes, Flonne Winnard, Paul Raman, Venu |
| description | The homeotic gene HOXA5 has been shown to play an important role in breast tumorigenesis. We have shown that loss of p53 correlated with loss of a developmentally regulated transcription factor, HOXA5, in primary breast cancer. Searching for potential protein interacting partners we found that HOXA5 binds to an anti-apoptotic protein, Twist. Furthermore, Twist-overexpressing MCF-7 cells displayed a deregulated p53 response to γ-radiation and decreased regulation of downstream target genes. Using a p53-promoter-reporter system, we demonstrated that HOXA5 could partially restore the inhibitory effects of Twist on p53 target genes. These effects are likely mediated through both the transcriptional up-regulation of p53 and the protein-protein interaction between HOXA5 and Twist. Thus, the loss of HOXA5 expression could lead to the functional activation of Twist resulting in aberrant cell cycle regulation and promoting breast carcinogenesis. |
| doi_str_mv | 10.1074/jbc.M411018200 |
| format | Article |
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We have shown that loss of p53 correlated with loss of a developmentally regulated transcription factor, HOXA5, in primary breast cancer. Searching for potential protein interacting partners we found that HOXA5 binds to an anti-apoptotic protein, Twist. Furthermore, Twist-overexpressing MCF-7 cells displayed a deregulated p53 response to γ-radiation and decreased regulation of downstream target genes. Using a p53-promoter-reporter system, we demonstrated that HOXA5 could partially restore the inhibitory effects of Twist on p53 target genes. These effects are likely mediated through both the transcriptional up-regulation of p53 and the protein-protein interaction between HOXA5 and Twist. Thus, the loss of HOXA5 expression could lead to the functional activation of Twist resulting in aberrant cell cycle regulation and promoting breast carcinogenesis.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M411018200</identifier><identifier>PMID: 15545268</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Base Sequence ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cell Line, Tumor ; Gamma Rays ; Homeodomain Proteins - metabolism ; Humans ; Immunoprecipitation ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Phosphoproteins - metabolism ; Promoter Regions, Genetic ; RNA, Small Interfering - metabolism ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Tumor Suppressor Protein p53 - chemistry ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; Twist-Related Protein 1 ; Two-Hybrid System Techniques</subject><ispartof>The Journal of biological chemistry, 2005-01, Vol.280 (3), p.2294-2299</ispartof><rights>2005 © 2005 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-c56c0b3385b3e54a71fe38c40104fce025776448e255b766d42ed438d38060403</citedby><cites>FETCH-LOGICAL-c440t-c56c0b3385b3e54a71fe38c40104fce025776448e255b766d42ed438d38060403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15545268$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stasinopoulos, Ioannis A.</creatorcontrib><creatorcontrib>Mironchik, Yelena</creatorcontrib><creatorcontrib>Raman, Ana</creatorcontrib><creatorcontrib>Wildes, Flonne</creatorcontrib><creatorcontrib>Winnard, Paul</creatorcontrib><creatorcontrib>Raman, Venu</creatorcontrib><title>HOXA5-Twist Interaction Alters p53 Homeostasis in Breast Cancer Cells</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The homeotic gene HOXA5 has been shown to play an important role in breast tumorigenesis. We have shown that loss of p53 correlated with loss of a developmentally regulated transcription factor, HOXA5, in primary breast cancer. Searching for potential protein interacting partners we found that HOXA5 binds to an anti-apoptotic protein, Twist. Furthermore, Twist-overexpressing MCF-7 cells displayed a deregulated p53 response to γ-radiation and decreased regulation of downstream target genes. Using a p53-promoter-reporter system, we demonstrated that HOXA5 could partially restore the inhibitory effects of Twist on p53 target genes. These effects are likely mediated through both the transcriptional up-regulation of p53 and the protein-protein interaction between HOXA5 and Twist. Thus, the loss of HOXA5 expression could lead to the functional activation of Twist resulting in aberrant cell cycle regulation and promoting breast carcinogenesis.</description><subject>Base Sequence</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Line, Tumor</subject><subject>Gamma Rays</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Phosphoproteins - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Tumor Suppressor Protein p53 - chemistry</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Twist-Related Protein 1</subject><subject>Two-Hybrid System Techniques</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kD1PAkEQhjdGo4i2luZiYXc4-3W3lEhQSDA0mNBt7vbmZMl94O4h8d-7BBIqp5kpnvfN5CHkgcKAQipeNrkZfAhKgSoGcEF6FBSPuaSrS9IDYDQeMqluyK33GwgjhvSa3FAphWSJ6pHJdLEayXi5t76LZk2HLjOdbZtoVIXbR1vJo2lbY-u7zFsf2SZ6dZgFeJw1Bl00xqryd-SqzCqP96fdJ59vk-V4Gs8X77PxaB4bIaCLjUwM5JwrmXOUIktpiVwZARREaRCYTNNECIVMyjxNkkIwLARXBVeQgADeJ8_H3q1rv3foO11bb8IHWYPtzmuaSikTfgAHR9C41nuHpd46W2fuV1PQB3E6iNNncSHweGre5TUWZ_xkKgBPR2Btv9Z761DntjVrrDVToLlmbCgCpI4QBgk_Fp32xmLwVISA6XTR2v8e-AOB0oRL</recordid><startdate>20050121</startdate><enddate>20050121</enddate><creator>Stasinopoulos, Ioannis A.</creator><creator>Mironchik, Yelena</creator><creator>Raman, Ana</creator><creator>Wildes, Flonne</creator><creator>Winnard, Paul</creator><creator>Raman, Venu</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</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>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20050121</creationdate><title>HOXA5-Twist Interaction Alters p53 Homeostasis in Breast Cancer Cells</title><author>Stasinopoulos, Ioannis A. ; 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We have shown that loss of p53 correlated with loss of a developmentally regulated transcription factor, HOXA5, in primary breast cancer. Searching for potential protein interacting partners we found that HOXA5 binds to an anti-apoptotic protein, Twist. Furthermore, Twist-overexpressing MCF-7 cells displayed a deregulated p53 response to γ-radiation and decreased regulation of downstream target genes. Using a p53-promoter-reporter system, we demonstrated that HOXA5 could partially restore the inhibitory effects of Twist on p53 target genes. These effects are likely mediated through both the transcriptional up-regulation of p53 and the protein-protein interaction between HOXA5 and Twist. 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| subjects | Base Sequence Breast Neoplasms - metabolism Breast Neoplasms - pathology Cell Line, Tumor Gamma Rays Homeodomain Proteins - metabolism Humans Immunoprecipitation Nuclear Proteins - genetics Nuclear Proteins - metabolism Phosphoproteins - metabolism Promoter Regions, Genetic RNA, Small Interfering - metabolism Transcription Factors - genetics Transcription Factors - metabolism Tumor Suppressor Protein p53 - chemistry Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Twist-Related Protein 1 Two-Hybrid System Techniques |
| title | HOXA5-Twist Interaction Alters p53 Homeostasis in Breast Cancer Cells |
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