Transcriptional Regulation of YWHAZ, the Gene Encoding 14-3-3ζ
| Autor: | Fadlo R. Khuri, Andrea L. Kasinski, Haian Fu, Xue-Yuan Dong, Jeremy M. Boss |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Transcription
Genetic Response element lcsh:Medicine Regulatory Sequences Nucleic Acid Biochemistry Cell Signaling Molecular Cell Biology Transcriptional regulation RNA Isoforms lcsh:Science Cyclic AMP Response Element-Binding Protein Promoter Regions Genetic Regulation of gene expression Genetics Expressed sequence tag Multidisciplinary Nuclear Proteins Exons Regulatory sequence YWHAZ Research Article Signal Transduction Protein Binding Transcriptional Activation DNA transcription Molecular Sequence Data Biology Cell Line Molecular Genetics Humans RNA Messenger Protein Interactions Gene Oncogenic Signaling Activating Transcription Factor 1 Biology and life sciences Base Sequence Tumor Necrosis Factor-alpha lcsh:R Alternative splicing Proteins Computational Biology Cell Biology Alternative Splicing 14-3-3 Proteins Gene Expression Regulation Protein Biosynthesis lcsh:Q Transcriptional Signaling Gene expression 5' Untranslated Regions Sequence Alignment |
| Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 4, p e93480 (2014) |
| ISSN: | 1932-6203 |
| Popis: | Aberrant expression of oncogenic 14-3-3 proteins is correlated with poor survival of cancer patients. While the underlying mechanism of the abnormal expression in tumors remains elusive for the six oncogenic 14-3-3 isoforms; the potential involvement of a transcriptional component has been suggested. Unfortunately, little experimental data has been reported to support this hypothesis. In this study we describe the genetic structure of YWHAZ, the gene encoding 14-3-3ζ, including the identification of previously unreported transcript variants. In total, five transcript variants were revealed and their expressions confirmed in a panel of cell lines. Expressed sequence tag (EST) database mining and in vitro rapid-amplification of cDNA ends (RACE) confirmed that one variant, 1c, represents >80% of the expressed transcripts, which is also the most efficiently translated. An analysis of the proximal promoter of this variant revealed a functional Cyclic-AMP Response Element (CRE). Factors that bound to the CRE element were recognized through fractionation and subsequent EMSAs. This analysis identified CREB and ATF-1 as the trans-interacting factors. Cell-based assays confirm that ATF-1, and to a lesser extent CREB, bind the endogenous YWHAZ promoter especially under TNF-α stimulating conditions. In support of a role of ATF-1 in the regulation of YWHAZ, silencing of ATF-1 resulted in a marked reduction in two of the five YWHAZ transcripts. These data suggest a novel mechanism for the transcriptional regulation of a major pro-survival gene, YWHAZ, by ATF-1. |
| Databáze: | OpenAIRE |
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