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The PRR11-SKA2 Bidirectional Transcription Unit Is Negatively Regulated by p53 through NF-Y in Lung Cancer Cells
Wang, Yitao1,2; Weng, Huali1,2; Zhang, Ying1,2; Long, Yinjiang1,2; Li, Yi1,2; Niu, Yulong2; Song, Fangzhou1,2; Bu, Youquan1,2
2017-03
Source PublicationINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN1422-0067
Volume18Issue:3
AbstractWe previously identified proline-rich protein 11 (PRR11) as a novel cancer-related gene that is implicated in the regulation of cell cycle and tumorigenesis. Our recent study demonstrated that PRR11 and its adjacent gene, kinetochore associated 2 (SKA2), constitute a classic head-to-head gene pair that is coordinately regulated by nuclear factor Y (NF-Y). In the present study, we further show that the PRR11-SKA2 bidirectional transcription unit is an indirect target of the tumor suppressor p53. A luciferase reporter assay revealed that overexpression of wild type p53, but not mutant p53, significantly represses the basal activity and NF-Y mediated transactivation of the PRR11-SKA2 bidirectional promoter. Deletion and mutation analysis of the PRR11-SKA2 promoter revealed that p53-mediated PRR11-SKA2 repression is dependent on the presence of functional NF-Y binding sites. Furthermore, a co-immunoprecipitation assay revealed that p53 associates with NF-Y in lung cancer cells, and a chromatin immunoprecipitation assay showed that p53 represses PRR11-SKA2 transcription by reducing the binding amount of NF-Y in the PRR11-SKA2 promoter region. Consistently, the ability of p53 to downregulate PRR11-SKA2 transcription was significantly attenuated upon siRNA-mediated depletion of nuclear factor Y subunit beta (NF-YB). Notably, lung cancer patients with lower expression of either PRR11 or SKA2 along with wild type p53 exhibited the best overall survival compared with others with p53 mutation and/or higher expression of either PRR11 or SKA2. Taken together, our results demonstrate that p53 negatively regulates the expression of the PRR11-SKA2 bidirectional transcription unit through NF-Y, suggesting that the inability to repress the PRR11-SKA2 bidirectional transcription unit after loss of p53 might contribute to tumorigenesis.
Keywordp53 NF-Y bidirectional promoter PRR11 SKA2 lung cancer
DOI10.3390/ijms18030534
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Chemistry
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Multidisciplinary
WOS IDWOS:000396253700065
PublisherMDPI AG
The Source to ArticleWOS
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Cited Times [WOS]:6   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Chongqing Med Univ, Dept Biochem & Mol Biol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China;
2.Chongqing Med Univ, Mol Med & Canc Res Ctr, Chongqing 400016, Peoples R China
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Wang, Yitao,Weng, Huali,Zhang, Ying,et al. The PRR11-SKA2 Bidirectional Transcription Unit Is Negatively Regulated by p53 through NF-Y in Lung Cancer Cells[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2017,18(3).
APA Wang, Yitao.,Weng, Huali.,Zhang, Ying.,Long, Yinjiang.,Li, Yi.,...&Bu, Youquan.(2017).The PRR11-SKA2 Bidirectional Transcription Unit Is Negatively Regulated by p53 through NF-Y in Lung Cancer Cells.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,18(3).
MLA Wang, Yitao,et al."The PRR11-SKA2 Bidirectional Transcription Unit Is Negatively Regulated by p53 through NF-Y in Lung Cancer Cells".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 18.3(2017).
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