Coupled alteration of transcription and splicing by a single oncogene: Boosting the effect on cyclin D1 activity
In cancer cells, gene expression is altered at the levels of transcription and mRNA maturation, with many splice variants being associated with cancer. Splicing is tightly connected to transcription and can be affected by transcription elongation dynamics. Moreover, various transcriptional coregulat...
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| Veröffentlicht in: | Cell cycle (Georgetown, Tex.) Tex.), 2008-08, Vol.7 (15), p.2299-2305 |
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| creator | Sanchez, Gabriel Delattre, Olivier Auboeuf, Didier Dutertre, Martin |
| description | In cancer cells, gene expression is altered at the levels of transcription and mRNA maturation, with many splice variants being associated with cancer. Splicing is tightly connected to transcription and can be affected by transcription elongation dynamics. Moreover, various transcriptional coregulators that are altered in cancer, such as the proto-oncogene EWS, are thought to play a role in splicing. A recent study shows that an alteration of EWS in Ewing sarcoma alters the dynamics of RNA polymerase II over the CCND1 proto-oncogene encoding cyclin D1, leading to an increase in its transcription and to an alteration of splicing that results in high levels of the oncogenic cyclin D1b splice isoform. The cyclin D1b isoform is highly expressed in Ewing sarcoma cells and tumors and stimulates Ewing sarcoma cell growth. Thus, alterations of transcriptional regulators in disease may lead to splicing alterations. We review these data and discuss how this concept may apply to various factors that are altered in cancer. |
| doi_str_mv | 10.4161/cc.6445 |
| format | Article |
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Splicing is tightly connected to transcription and can be affected by transcription elongation dynamics. Moreover, various transcriptional coregulators that are altered in cancer, such as the proto-oncogene EWS, are thought to play a role in splicing. A recent study shows that an alteration of EWS in Ewing sarcoma alters the dynamics of RNA polymerase II over the CCND1 proto-oncogene encoding cyclin D1, leading to an increase in its transcription and to an alteration of splicing that results in high levels of the oncogenic cyclin D1b splice isoform. The cyclin D1b isoform is highly expressed in Ewing sarcoma cells and tumors and stimulates Ewing sarcoma cell growth. Thus, alterations of transcriptional regulators in disease may lead to splicing alterations. 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Delattre, Olivier ; Auboeuf, Didier ; Dutertre, Martin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c395t-755df68c4bde9001bd930aab0f9c970e8f6d363e2cf9e8d60717b775715669663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Binding</topic><topic>Biology</topic><topic>Bioscience</topic><topic>Bone Neoplasms - genetics</topic><topic>Calcium</topic><topic>Cancer</topic><topic>Cell</topic><topic>Cycle</topic><topic>Cyclin D1 - genetics</topic><topic>Cyclin D1 - metabolism</topic><topic>Cyclin D1 - physiology</topic><topic>Humans</topic><topic>Landes</topic><topic>Models, Biological</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - metabolism</topic><topic>Oncogene Proteins, Fusion - genetics</topic><topic>Oncogene Proteins, Fusion - physiology</topic><topic>Oncogenes - physiology</topic><topic>Organogenesis</topic><topic>Proteins</topic><topic>Proto-Oncogene Protein c-fli-1 - genetics</topic><topic>Proto-Oncogene Protein c-fli-1 - physiology</topic><topic>RNA Splicing - genetics</topic><topic>RNA-Binding Protein EWS - genetics</topic><topic>RNA-Binding Protein EWS - physiology</topic><topic>Sarcoma, Ewing - genetics</topic><topic>Trans-Activators - physiology</topic><topic>Transcription, Genetic - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sanchez, Gabriel</creatorcontrib><creatorcontrib>Delattre, Olivier</creatorcontrib><creatorcontrib>Auboeuf, Didier</creatorcontrib><creatorcontrib>Dutertre, Martin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cell cycle (Georgetown, Tex.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sanchez, Gabriel</au><au>Delattre, Olivier</au><au>Auboeuf, Didier</au><au>Dutertre, Martin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Coupled alteration of transcription and splicing by a single oncogene: Boosting the effect on cyclin D1 activity</atitle><jtitle>Cell cycle (Georgetown, Tex.)</jtitle><addtitle>Cell Cycle</addtitle><date>2008-08-01</date><risdate>2008</risdate><volume>7</volume><issue>15</issue><spage>2299</spage><epage>2305</epage><pages>2299-2305</pages><issn>1538-4101</issn><eissn>1551-4005</eissn><abstract>In cancer cells, gene expression is altered at the levels of transcription and mRNA maturation, with many splice variants being associated with cancer. 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| subjects | Animals Binding Biology Bioscience Bone Neoplasms - genetics Calcium Cancer Cell Cycle Cyclin D1 - genetics Cyclin D1 - metabolism Cyclin D1 - physiology Humans Landes Models, Biological Neoplasms - genetics Neoplasms - metabolism Oncogene Proteins, Fusion - genetics Oncogene Proteins, Fusion - physiology Oncogenes - physiology Organogenesis Proteins Proto-Oncogene Protein c-fli-1 - genetics Proto-Oncogene Protein c-fli-1 - physiology RNA Splicing - genetics RNA-Binding Protein EWS - genetics RNA-Binding Protein EWS - physiology Sarcoma, Ewing - genetics Trans-Activators - physiology Transcription, Genetic - genetics |
| title | Coupled alteration of transcription and splicing by a single oncogene: Boosting the effect on cyclin D1 activity |
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