| Defining the regulatory elements in the proximal promoter of DeltaNp63 in keratinocytes: Potential roles for Sp1/Sp3, NF-Y, and p63. | |
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MedLine Citation:
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PMID: 16645595 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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p63, a homolog of the tumor suppressor p53, plays an important role in the formation of stratified epithelium such as those in the epidermis of the skin. The p63 gene gives rise to multiple functionally distinct protein isoforms, including the DeltaNp63 class of isoforms, which lacks the N-terminal transactivation domain and is synthesized from an internal promoter. DeltaNp63 proteins are the predominant isoforms expressed in keratinocytes and are thought to be important for maintenance of the proliferative capacity of these cells. Here, we have examined the transcriptional control mechanisms that govern the expression DeltaNp63 in keratinocytes. We first performed DNase I hypersensitive site mapping and demonstrated that the promoter region of DeltaNp63 is in open chromatin state in keratinocytes. To identify the cis-elements that regulate DeltaNp63, we have performed transient transfection assays in keratinocytes with several DeltaNp63 promoter constructs. This identified a short evolutionarily conserved fragment that harbors most of the transcriptional activity of the DeltaNp63 promoter. Biochemical studies of this element have revealed critical roles for CCAAT-box-binding factor (CBF/NF-Y) and Sp1/Sp3 family of proteins. In addition, our data suggest that DeltaNp63 is recruited to and can activate its own promoter, possibly through protein-protein interactions, thus providing an auto-regulatory loop of self-regulation. These studies support the notion that unique and distinct pathways control the expression of individual p53 family members and their various isoforms. |
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Authors:
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Rose-Anne Romano; Barbara Birkaya; Satrajit Sinha |
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Publication Detail:
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Type: Journal Article Date: 2006-04-27 |
Journal Detail:
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Title: The Journal of investigative dermatology Volume: 126 ISSN: 0022-202X ISO Abbreviation: J. Invest. Dermatol. Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-06-16 Completed Date: 2006-08-01 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 0426720 Medline TA: J Invest Dermatol Country: United States |
Other Details:
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Languages: eng Pagination: 1469-79 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, State University of New York at Buffalo, Buffalo, New York, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Base Sequence CCAAT-Binding Factor / genetics, physiology Cell Line Cell Line, Tumor Cell Proliferation Chromatin / chemistry DNA / analysis, genetics DNA Mutational Analysis Gene Expression Regulation Hela Cells Humans Keratinocytes / chemistry, cytology, physiology* Mice Molecular Sequence Data NIH 3T3 Cells Phosphoproteins / analysis, genetics*, physiology Potoroidae Promoter Regions, Genetic / genetics*, physiology Protein Binding Protein Isoforms / analysis, physiology Regulatory Elements, Transcriptional / genetics*, physiology Sp1 Transcription Factor / genetics, physiology* Sp3 Transcription Factor / genetics, physiology* Trans-Activators / analysis, genetics*, physiology Transfection |
| Chemical | |
Reg. No./Substance:
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0/CCAAT-Binding Factor; 0/Chromatin; 0/Phosphoproteins; 0/Protein Isoforms; 0/Sp1 Transcription Factor; 0/Sp3 protein, mouse; 0/Trans-Activators; 0/Trp63 protein, mouse; 148710-94-5/Sp3 Transcription Factor; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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