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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >An expression screen reveals modulators of class Ⅱ histone deacetylase phosphorylation
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An expression screen reveals modulators of class Ⅱ histone deacetylase phosphorylation

机译：表达筛选揭示了Ⅱ类组蛋白脱乙酰基酶磷酸化的调节剂

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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 phos-phorylated 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.
机译：Ⅱ类组蛋白脱乙酰基酶（HDACs）通过与多种转录因子和共表达因子相关联来抑制转录。 Ⅱ类HDAC的N端延伸中一组保守的丝氨酸残基的磷酸化产生14-3-3伴侣蛋白的结合位点，从而触发这些HDAC的核输出，从而以信号依赖的方式抑制特定的靶基因。为了鉴定控制II类HDAC5 HDAC5磷酸化的细胞内信号通路，我们设计了一个真核cDNA表达筛选，其中表达了GAL4依赖的荧光素酶报告基因，其GAL4的DNA结合域与HDAC5的N端延伸融合VP16转录激活域融合到14-3-3。用cDNA表达文库转染COS细胞可通过编码HDAC5激酶或此类激酶调节剂的cDNA激活萤光素酶表达，从而使磷酸化GAL4-HDAC5募集14-3-3-VP16，从而重建功能性转录复合物。我们的结果揭示了多种信号通路，它们收敛于HDAC5中的信号响应磷酸化位点，从而使HDAC5能够将细胞外信号连接至基因组。

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