Juglone, an inhibitor of the peptidyl-prolyl isomerase Pin1, also directly blocks transcription
Juglone, an inhibitor of the peptidyl-prolyl isomerase Pin1, also directly blocks transcription
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DOI：
10.1093/nar/29.3.767
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发表时间：
2001-02-01
影响因子：
14.9
通讯作者：
Price, DH
中科院分区：
文献类型：
--
作者：
Chao, SH;Greenleaf, AL;Price, DH
RNA聚合酶II大亚基的C末端结构域（CTD）在转录和RNA加工中起作用。酵母ESS 1是一种肽基脯氨酰顺/反异构酶，参与RNA加工并与CTD结合。使用几种类型的测定，我们无法找到任何证据的影响Pin 1，人类同源的ESS 1，在体外转录RNA聚合酶II或在体内的报告基因的表达。然而，Pin 1的抑制剂，5-羟基-1，4-萘醌（胡桃醌），通过RNA聚合酶II阻断转录。不像N-乙基马来酰亚胺，抑制RNA聚合酶II的转录的所有阶段，胡桃醌破坏的功能preinitiation复合物的形成，通过修饰巯基，但没有任何显着的影响，无论是启动或延长。RNA聚合酶I和III，但不是T7 RNA聚合酶，被胡桃醌抑制。胡桃醌的主要靶点尚未明确确定，尽管在单链DNA的因子非依赖性转录过程中RNA聚合酶II的抑制作用提示了聚合酶本身的一个位点。由于其独特的抑制性能胡桃醌应证明在体外研究转录有用。
The C-terminal domain (CTD) of the large subunit of RNA polymerase II plays a role in transcription and RNA processing. Yeast ESS1, a peptidyl-prolyl cis/trans isomerase, is involved in RNA processing and can associate with the CTD. Using several types of assays we could not find any evidence of an effect of Pin1, the human homolog of ESS1, on transcription by RNA polymerase II in vitro or on the expression of a reporter gene in vivo. However, an inhibitor of Pin1,5-hydroxy-1,4-naphthoquinone (juglone), blocked transcription by RNA polymerase II. Unlike N-ethyl-maleimide, which inhibited all phases of transcription by RNA polymerase II, juglone disrupted the formation of functional preinitiation complexes by modifying sulfhydryl groups but did not have any significant effect on either initiation or elongation. Both RNA polymerases I and III, but not T7 RNA polymerase, were inhibited by juglone. The primary target of juglone has not been unambiguously identified, although a site on the polymerase itself is suggested by inhibition of RNA polymerase II during factor-independent transcription of single-stranded DNA. Because of its unique inhibitory properties juglone should prove useful in studying transcription in vitro.