دورية أكاديمية
Isogenic human cell lines for drug discovery: regulation of target gene expression by engineered zinc-finger protein transcription factors.
| العنوان: | Isogenic human cell lines for drug discovery: regulation of target gene expression by engineered zinc-finger protein transcription factors. |
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| المؤلفون: | Liu PQ; Sangamo BioSciences, Inc., Richmond, CA 94804, USA., Tan S, Mendel MC, Murrills RJ, Bhat BM, Schlag B, Samuel R, Matteo JJ, de la Rosa R, Howes K, Reik A, Case CC, Bex FJ, Young K, Gregory PD |
| المصدر: | Journal of biomolecular screening [J Biomol Screen] 2005 Jun; Vol. 10 (4), pp. 304-13. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Sage Publications Country of Publication: United States NLM ID: 9612112 Publication Model: Print Cited Medium: Print ISSN: 1087-0571 (Print) Linking ISSN: 10870571 NLM ISO Abbreviation: J Biomol Screen Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2004- > : Thousand Oaks, CA : Sage Publications Original Publication: Larchmont, NY : Mary Ann Liebert, Inc., c1996- |
| مواضيع طبية MeSH: | Gene Expression Regulation* , Protein Engineering* , Zinc Fingers*, Transcription Factors/*physiology, Amino Acid Sequence ; Base Sequence ; Cell Line ; DNA Primers ; Humans ; Molecular Sequence Data ; RNA, Messenger/genetics ; Receptor, Parathyroid Hormone, Type 1/chemistry ; Receptor, Parathyroid Hormone, Type 1/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors/chemistry |
| مستخلص: | Isogenic cell lines differing only in the expression of the protein of interest provide the ideal platform for cell-based screening. However, related natural lines differentially expressing the therapeutic target of choice are rare. Here the authors report a strategy for drug screening employing isogenic human cell lines in which the expression of the target protein is regulated by a gene-specific engineered zinc-finger protein (ZFP) transcription factor (TF). To demonstrate this approach, a ZFP TF activator of the human parathyroid hormone receptor 1 (PTHR1) gene was identified and introduced into HEK293 cells (negative for PTHR1). Following induction of ZFP TF expression, this cell line produced functional PTHR1 protein, resulting in a robust and ligand-specific cyclic adenosine monophosphate (cAMP) response. Reciprocally, the natural expression of PTHR1 observed in SAOS2 cells was dramatically reduced by the introduction of the appropriate PTHR1-specific ZFP TF repressor. Moreover, this ZFP-driven PTHR1 repression selectively eliminated the functional cAMP response invoked by known ligands of PTHR1. These data establish ZFP TF-generated isogenic lines as a general approach for the identification of therapeutic agents specific for the target gene of interest. |
| المشرفين على المادة: | 0 (DNA Primers) 0 (RNA, Messenger) 0 (Receptor, Parathyroid Hormone, Type 1) 0 (Transcription Factors) |
| تواريخ الأحداث: | Date Created: 20050621 Date Completed: 20051004 Latest Revision: 20110523 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1177/1087057104272663 |
| PMID: | 15964931 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1087-0571 |
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| DOI: | 10.1177/1087057104272663 |