cis-Acting elements and trans-acting factors in the transcriptional regulation of raf kinase inhibitory protein expression.
The Raf kinase inhibitory protein (RKIP) is down-regulated in multiple types of human cancers. Decreased RKIP transcription activity may be one of the major mechanisms responsible for the downregulation of RKIP expression in human diseases. To test this hypothesis, we need to gain basic knowledge of...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3873293?pdf=render |
| _version_ | 1818137915697397760 |
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| author | Boyan Zhang Ou Wang Jingchao Qin Shuaishuai Liu Sheng Sun Huitu Liu Jian Kuang Guohua Jiang Wei Zhang |
| author_facet | Boyan Zhang Ou Wang Jingchao Qin Shuaishuai Liu Sheng Sun Huitu Liu Jian Kuang Guohua Jiang Wei Zhang |
| author_sort | Boyan Zhang |
| collection | DOAJ |
| description | The Raf kinase inhibitory protein (RKIP) is down-regulated in multiple types of human cancers. Decreased RKIP transcription activity may be one of the major mechanisms responsible for the downregulation of RKIP expression in human diseases. To test this hypothesis, we need to gain basic knowledge of the transcriptional regulation of RKIP. To achieve this objective, we made a systematic effort to identify cis-acting elements and trans-acting factors that control RKIP promoter activity. We found that full RKIP promoter activity requires the region -56 to +261 relative to the transcription start site. Within the full promoter region, there are two motifs rich in G/C that responded to transcription factor Sp1, one cAMP-responsive element that responded to the transcription factor CREB, and one docking site for the histone acetylase p300. In human melanoma A375 cells and human cervical cancer HeLa cells, mutation or deletion of each of these cis-acting elements decreased promoter activity. In A375 cells, knockdown of the corresponding transcription factors Sp1, CREB, or p300 decreased RKIP promoter activity, whereas overexpression of CREB and p300 increased RKIP promoter activity. The results obtained with HeLa cells also supported the idea that Sp1 and CREB play positive roles in the regulation of RKIP transcription. These findings suggest that regulators of the expression or activity of Sp1, CREB, and p300 are involved in regulating RKIP transcription. |
| first_indexed | 2024-12-11T10:03:53Z |
| format | Article |
| id | doaj.art-f3558da07c434f948c7c943be2cd52b4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T10:03:53Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f3558da07c434f948c7c943be2cd52b42022-12-22T01:12:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8309710.1371/journal.pone.0083097cis-Acting elements and trans-acting factors in the transcriptional regulation of raf kinase inhibitory protein expression.Boyan ZhangOu WangJingchao QinShuaishuai LiuSheng SunHuitu LiuJian KuangGuohua JiangWei ZhangThe Raf kinase inhibitory protein (RKIP) is down-regulated in multiple types of human cancers. Decreased RKIP transcription activity may be one of the major mechanisms responsible for the downregulation of RKIP expression in human diseases. To test this hypothesis, we need to gain basic knowledge of the transcriptional regulation of RKIP. To achieve this objective, we made a systematic effort to identify cis-acting elements and trans-acting factors that control RKIP promoter activity. We found that full RKIP promoter activity requires the region -56 to +261 relative to the transcription start site. Within the full promoter region, there are two motifs rich in G/C that responded to transcription factor Sp1, one cAMP-responsive element that responded to the transcription factor CREB, and one docking site for the histone acetylase p300. In human melanoma A375 cells and human cervical cancer HeLa cells, mutation or deletion of each of these cis-acting elements decreased promoter activity. In A375 cells, knockdown of the corresponding transcription factors Sp1, CREB, or p300 decreased RKIP promoter activity, whereas overexpression of CREB and p300 increased RKIP promoter activity. The results obtained with HeLa cells also supported the idea that Sp1 and CREB play positive roles in the regulation of RKIP transcription. These findings suggest that regulators of the expression or activity of Sp1, CREB, and p300 are involved in regulating RKIP transcription.http://europepmc.org/articles/PMC3873293?pdf=render |
| spellingShingle | Boyan Zhang Ou Wang Jingchao Qin Shuaishuai Liu Sheng Sun Huitu Liu Jian Kuang Guohua Jiang Wei Zhang cis-Acting elements and trans-acting factors in the transcriptional regulation of raf kinase inhibitory protein expression. PLoS ONE |
| title | cis-Acting elements and trans-acting factors in the transcriptional regulation of raf kinase inhibitory protein expression. |
| title_full | cis-Acting elements and trans-acting factors in the transcriptional regulation of raf kinase inhibitory protein expression. |
| title_fullStr | cis-Acting elements and trans-acting factors in the transcriptional regulation of raf kinase inhibitory protein expression. |
| title_full_unstemmed | cis-Acting elements and trans-acting factors in the transcriptional regulation of raf kinase inhibitory protein expression. |
| title_short | cis-Acting elements and trans-acting factors in the transcriptional regulation of raf kinase inhibitory protein expression. |
| title_sort | cis acting elements and trans acting factors in the transcriptional regulation of raf kinase inhibitory protein expression |
| url | http://europepmc.org/articles/PMC3873293?pdf=render |
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