Pdcd4 directly binds the coding region of c-myb mRNA and suppresses its translation
Pdcd4 is a novel tumor suppressor protein that functions in the nucleus and the cytoplasm, and appears to be involved in the regulation of transcription and translation. In the cytoplasm, Pdcd4 has been implicated in the suppression of translation of mRNAs containing structured 5′-untranslated regio...
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| Veröffentlicht in: | Oncogene 2011-12, Vol.30 (49), p.4864-4873 |
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| creator | Singh, P Wedeken, L Waters, L C Carr, M D Klempnauer, K-H |
| description | Pdcd4 is a novel tumor suppressor protein that functions in the nucleus and the cytoplasm, and appears to be involved in the regulation of transcription and translation. In the cytoplasm, Pdcd4 has been implicated in the suppression of translation of mRNAs containing structured 5′-untranslated regions; however, the mechanisms that recruit Pdcd4 to specific target mRNAs and the identities of these mRNAs are mostly unknown. In this study, we have identified c-
myb
mRNA as the first natural translational target mRNA of Pdcd4. We have found that translational suppression of c-
myb
mRNA by Pdcd4 is dependent on sequences located within the c-
myb
-coding region. Furthermore, we have found that the N-terminal domain of Pdcd4 has an important role in targeting Pdcd4 to c-
myb
RNA by mediating preferential RNA binding to the Pdcd4-responsive region of c-
myb
mRNA. Overall, our work demonstrates for the first time that Pdcd4 is directly involved in translational suppression of a natural mRNA and provides the first evidence for a key role of the RNA-binding domain in targeting Pdcd4 to a specific mRNA. |
| doi_str_mv | 10.1038/onc.2011.202 |
| format | Article |
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myb
mRNA as the first natural translational target mRNA of Pdcd4. We have found that translational suppression of c-
myb
mRNA by Pdcd4 is dependent on sequences located within the c-
myb
-coding region. Furthermore, we have found that the N-terminal domain of Pdcd4 has an important role in targeting Pdcd4 to c-
myb
RNA by mediating preferential RNA binding to the Pdcd4-responsive region of c-
myb
mRNA. Overall, our work demonstrates for the first time that Pdcd4 is directly involved in translational suppression of a natural mRNA and provides the first evidence for a key role of the RNA-binding domain in targeting Pdcd4 to a specific mRNA.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/onc.2011.202</identifier><identifier>PMID: 21643008</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>5' Untranslated Regions ; 631/337/574 ; 631/45/612/1244 ; 631/67/395 ; Animals ; Apoptosis ; Apoptosis Regulatory Proteins - chemistry ; Apoptosis Regulatory Proteins - metabolism ; Biological and medical sciences ; c-Myb protein ; Cancer ; Cell Biology ; Cell Line ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Chickens ; Cytoplasm ; Drug targeting ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gene regulation ; Genetic aspects ; Human Genetics ; Humans ; Internal Medicine ; Medicine ; Medicine & Public Health ; Messenger RNA ; Molecular and cellular biology ; Nuclei ; Oncology ; Open Reading Frames - genetics ; original-article ; Protein Binding ; Protein Biosynthesis - genetics ; Protein Structure, Tertiary ; Proto-Oncogene Proteins c-myb - biosynthesis ; Proto-Oncogene Proteins c-myb - genetics ; Proto-oncogenes ; Response Elements - genetics ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; RNA-Binding Proteins - chemistry ; RNA-Binding Proteins - metabolism ; RNA-protein interactions ; Substrate Specificity ; Transcription ; Translation ; Tumor suppressor genes ; Tumors</subject><ispartof>Oncogene, 2011-12, Vol.30 (49), p.4864-4873</ispartof><rights>Macmillan Publishers Limited 2011</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2011 Nature Publishing Group</rights><rights>Macmillan Publishers Limited 2011.</rights><rights>Copyright Nature Publishing Group Dec 8, 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c617t-c580414e3c77f3c960d881adf3ace31f395f37bad5e4d9d4071519ccf49af8a93</citedby><cites>FETCH-LOGICAL-c617t-c580414e3c77f3c960d881adf3ace31f395f37bad5e4d9d4071519ccf49af8a93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/onc.2011.202$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/onc.2011.202$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,778,782,27907,27908,41471,42540,51302</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25286478$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21643008$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Singh, P</creatorcontrib><creatorcontrib>Wedeken, L</creatorcontrib><creatorcontrib>Waters, L C</creatorcontrib><creatorcontrib>Carr, M D</creatorcontrib><creatorcontrib>Klempnauer, K-H</creatorcontrib><title>Pdcd4 directly binds the coding region of c-myb mRNA and suppresses its translation</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Pdcd4 is a novel tumor suppressor protein that functions in the nucleus and the cytoplasm, and appears to be involved in the regulation of transcription and translation. In the cytoplasm, Pdcd4 has been implicated in the suppression of translation of mRNAs containing structured 5′-untranslated regions; however, the mechanisms that recruit Pdcd4 to specific target mRNAs and the identities of these mRNAs are mostly unknown. In this study, we have identified c-
myb
mRNA as the first natural translational target mRNA of Pdcd4. We have found that translational suppression of c-
myb
mRNA by Pdcd4 is dependent on sequences located within the c-
myb
-coding region. Furthermore, we have found that the N-terminal domain of Pdcd4 has an important role in targeting Pdcd4 to c-
myb
RNA by mediating preferential RNA binding to the Pdcd4-responsive region of c-
myb
mRNA. Overall, our work demonstrates for the first time that Pdcd4 is directly involved in translational suppression of a natural mRNA and provides the first evidence for a key role of the RNA-binding domain in targeting Pdcd4 to a specific mRNA.</description><subject>5' Untranslated Regions</subject><subject>631/337/574</subject><subject>631/45/612/1244</subject><subject>631/67/395</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis Regulatory Proteins - chemistry</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>Biological and medical sciences</subject><subject>c-Myb protein</subject><subject>Cancer</subject><subject>Cell Biology</subject><subject>Cell Line</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Chickens</subject><subject>Cytoplasm</subject><subject>Drug targeting</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Gene regulation</subject><subject>Genetic aspects</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Messenger RNA</subject><subject>Molecular and cellular biology</subject><subject>Nuclei</subject><subject>Oncology</subject><subject>Open Reading Frames - genetics</subject><subject>original-article</subject><subject>Protein Binding</subject><subject>Protein Biosynthesis - genetics</subject><subject>Protein Structure, Tertiary</subject><subject>Proto-Oncogene Proteins c-myb - biosynthesis</subject><subject>Proto-Oncogene Proteins c-myb - genetics</subject><subject>Proto-oncogenes</subject><subject>Response Elements - genetics</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA-Binding Proteins - chemistry</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>RNA-protein interactions</subject><subject>Substrate Specificity</subject><subject>Transcription</subject><subject>Translation</subject><subject>Tumor suppressor genes</subject><subject>Tumors</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9ksuLFDEQxoMo7rh68yxBET3YY56dznFYdlVYVHycm0weY5buZDbpPsx_bw0zOiirBCqQ_KoqX-VD6CklS0p49zYnu2SEUgjsHlpQodpGSi3uowXRkjSacXaGHtV6QwhRmrCH6IzRVnBCugX6-tlZJ7CLxdtp2OF1TK7i6YfHNruYNrj4TcwJ54BtM-7WePzycYVNcrjO223xtfqK4wQpxaQ6mAngx-hBMEP1T477Ofp-dfnt4n1z_endh4vVdWNbqqbGyo4IKjy3SgVudUtc11HjAjfWcxq4loGrtXHSC6edIIpKqq0NQpvQGc3P0atD3W3Jt7OvUz_Gav0wmOTzXHtNqRYEkoB8_V-Swiw6LqSUgD7_C73Jc0mgo9cwT9ZKtq_34l8Qa0ET0Yp2J2pjBt_HFDIMye479yumJOOCyBao5R0ULOfHaHPyIcL5HwlvDgm25FqLD_22xNGUHcjo95bowRL93hIQGODPjm-d16N3v-FfHgDg5REw1ZohwEfaWE-cZF0r1J5rDlyFq7Tx5ST6zsY_ASijyP4</recordid><startdate>20111208</startdate><enddate>20111208</enddate><creator>Singh, P</creator><creator>Wedeken, L</creator><creator>Waters, L C</creator><creator>Carr, M D</creator><creator>Klempnauer, K-H</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>IQODW</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>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20111208</creationdate><title>Pdcd4 directly binds the coding region of c-myb mRNA and suppresses its translation</title><author>Singh, P ; Wedeken, L ; Waters, L C ; Carr, M D ; Klempnauer, K-H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c617t-c580414e3c77f3c960d881adf3ace31f395f37bad5e4d9d4071519ccf49af8a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>5' Untranslated Regions</topic><topic>631/337/574</topic><topic>631/45/612/1244</topic><topic>631/67/395</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis Regulatory Proteins - chemistry</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>Biological and medical sciences</topic><topic>c-Myb protein</topic><topic>Cancer</topic><topic>Cell Biology</topic><topic>Cell Line</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Chickens</topic><topic>Cytoplasm</topic><topic>Drug targeting</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Gene regulation</topic><topic>Genetic aspects</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Messenger RNA</topic><topic>Molecular and cellular biology</topic><topic>Nuclei</topic><topic>Oncology</topic><topic>Open Reading Frames - genetics</topic><topic>original-article</topic><topic>Protein Binding</topic><topic>Protein Biosynthesis - genetics</topic><topic>Protein Structure, Tertiary</topic><topic>Proto-Oncogene Proteins c-myb - biosynthesis</topic><topic>Proto-Oncogene Proteins c-myb - genetics</topic><topic>Proto-oncogenes</topic><topic>Response Elements - genetics</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA-Binding Proteins - chemistry</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>RNA-protein interactions</topic><topic>Substrate Specificity</topic><topic>Transcription</topic><topic>Translation</topic><topic>Tumor suppressor genes</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Singh, P</creatorcontrib><creatorcontrib>Wedeken, L</creatorcontrib><creatorcontrib>Waters, L C</creatorcontrib><creatorcontrib>Carr, M D</creatorcontrib><creatorcontrib>Klempnauer, K-H</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Singh, P</au><au>Wedeken, L</au><au>Waters, L C</au><au>Carr, M D</au><au>Klempnauer, K-H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pdcd4 directly binds the coding region of c-myb mRNA and suppresses its translation</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2011-12-08</date><risdate>2011</risdate><volume>30</volume><issue>49</issue><spage>4864</spage><epage>4873</epage><pages>4864-4873</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Pdcd4 is a novel tumor suppressor protein that functions in the nucleus and the cytoplasm, and appears to be involved in the regulation of transcription and translation. In the cytoplasm, Pdcd4 has been implicated in the suppression of translation of mRNAs containing structured 5′-untranslated regions; however, the mechanisms that recruit Pdcd4 to specific target mRNAs and the identities of these mRNAs are mostly unknown. In this study, we have identified c-
myb
mRNA as the first natural translational target mRNA of Pdcd4. We have found that translational suppression of c-
myb
mRNA by Pdcd4 is dependent on sequences located within the c-
myb
-coding region. Furthermore, we have found that the N-terminal domain of Pdcd4 has an important role in targeting Pdcd4 to c-
myb
RNA by mediating preferential RNA binding to the Pdcd4-responsive region of c-
myb
mRNA. Overall, our work demonstrates for the first time that Pdcd4 is directly involved in translational suppression of a natural mRNA and provides the first evidence for a key role of the RNA-binding domain in targeting Pdcd4 to a specific mRNA.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>21643008</pmid><doi>10.1038/onc.2011.202</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Oncogene, 2011-12, Vol.30 (49), p.4864-4873 |
| issn | 0950-9232 1476-5594 |
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| recordid | cdi_proquest_miscellaneous_911940151 |
| source | MEDLINE; Nature Journals Online; EZB-FREE-00999 freely available EZB journals; SpringerLink Journals - AutoHoldings |
| subjects | 5' Untranslated Regions 631/337/574 631/45/612/1244 631/67/395 Animals Apoptosis Apoptosis Regulatory Proteins - chemistry Apoptosis Regulatory Proteins - metabolism Biological and medical sciences c-Myb protein Cancer Cell Biology Cell Line Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Chickens Cytoplasm Drug targeting Fundamental and applied biological sciences. Psychology Gene expression Gene regulation Genetic aspects Human Genetics Humans Internal Medicine Medicine Medicine & Public Health Messenger RNA Molecular and cellular biology Nuclei Oncology Open Reading Frames - genetics original-article Protein Binding Protein Biosynthesis - genetics Protein Structure, Tertiary Proto-Oncogene Proteins c-myb - biosynthesis Proto-Oncogene Proteins c-myb - genetics Proto-oncogenes Response Elements - genetics RNA, Messenger - genetics RNA, Messenger - metabolism RNA-Binding Proteins - chemistry RNA-Binding Proteins - metabolism RNA-protein interactions Substrate Specificity Transcription Translation Tumor suppressor genes Tumors |
| title | Pdcd4 directly binds the coding region of c-myb mRNA and suppresses its translation |
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