文章基本信息

标题：An expression screen reveals modulators of class II histone deacetylase phosphorylation
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作者：Shurong Chang ; Svetlana Bezprozvannaya ; Shijie Li 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：23
页码：8120-8125
DOI：10.1073/pnas.0503275102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Class II histone deacetylases (HDACs) repress transcription by associating with a variety of transcription factors and corepressors. Phosphorylation of a set of conserved serine residues in the N-terminal extensions of class II HDACs creates binding sites for 14-3-3 chaperone proteins, which trigger nuclear export of these HDACs, thereby derepressing specific target genes in a signal-dependent manner. To identify intracellular signaling pathways that control phosphorylation of HDAC5, a class II HDAC, we designed a eukaryotic cDNA expression screen in which a GAL4-dependent luciferase reporter was expressed with the DNA-binding domain of GAL4 fused to the N-terminal extension of HDAC5 and the VP16 transcription activation domain fused to 14-3-3. The transfection of COS cells with cDNA expression libraries results in activation of luciferase expression by cDNAs encoding HDAC5 kinases or modulators of such kinases that enable phosphorylated GAL4-HDAC5 to recruit 14-3-3-VP16 with consequent reconstitution of a functional transcriptional complex. Our results reveal a remarkable variety of signaling pathways that converge on the signal-responsive phosphorylation sites in HDAC5, thereby enabling HDAC5 to connect extracellular signals to the genome.
关键词：endothelial differentiation genes ; lysophosphatidic acid receptors ; Rho signaling ; sphingosine-1 phosphate