Nuclear myosin II regulates the assembly of preinitiation complex for ICAM-1 gene transcription.

Nuclear myosin II regulates the assembly of preinitiation complex for ICAM-1 gene transcription.
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DOI:
10.1053/j.gastro.2009.03.040
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发表时间:
2009-09
期刊:
影响因子:
29.4
通讯作者:
Sarna SK
Sarna SK
中科院分区:
医学1区
文献类型:
--
作者:
Li Q;Sarna SK

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肌动蛋白-肌球蛋白II马达在肌肉和非肌肉细胞中将化学能转化为力/运动。调节轻链(MLC20)的磷酸化对这些马达的细胞质功能至关重要。我们不知道细胞核中的肌球蛋白II和肌动蛋白是否作为马达来产生相对运动,如RNA聚合酶II全酶和DNA之间的相对运动,以组装预起始复合体。本实验在原代培养的人结肠环状肌细胞和大鼠结肠环状肌条上进行。我们发现肌球蛋白II和α-和β-肌动蛋白存在于结肠平滑肌细胞的细胞核中。核肌球蛋白II与ICAM-1核心启动子区域的识别序列AGCTCC(−39/−34)连接。已知肌动蛋白与RNA聚合酶II形成复合体,它们与核骨架相连。MLC20的去磷酸化增加ICAM-1的转录,而它的磷酸化则降低ICAM-1的转录。结肠炎抑制核MLCK,增加核MLC20的非磷酸化形式,导致ICAM-1转录增强。1)肌球蛋白II是一个核心转录因子;2)核MLC20的磷酸化/去磷酸化导致肌球蛋白和肌动蛋白分子相互滑动,导致肌球蛋白II结合的DNA与肌动蛋白和核骨架结合的RNA聚合酶II全酶之间的相对运动。
Actin-myosin II motor converts chemical energy into force/motion in muscle and non-muscle cells. The phosphorylation of regulatory light chain (MLC20) is critical to the cytoplasmic functions of these motors. We do not know whether myosin II and actins in the nucleus function as motors to generate relative motion, such as that between RNA polymerase II holoenzyme and DNA, for assembly of the preinitiation complex. The experiments were performed on primary cultures of human colonic circular smooth muscle cells (HCCSMCs) and rat colonic circular muscle strips. We show that myosin II and α- and β-actins are present in the nuclei of colonic smooth muscle cells. The nuclear myosin II is tethered to recognition sequence AGCTCC (−39/−34) in the ICAM-1 core promoter region. The actins are known to complex with RNA polymerase II and they are tethered to the nucleoskeleton. The dephosphorylation of MLC20 increases the transcription of ICAM-1, whereas its phosphorylation decreases it. Colonic inflammation suppresses nuclear MLCK, which increases the unphosphorylated form of nuclear MLC20, resulting in enhanced transcription of ICAM-1. 1) Myosin II is a core transcription factor; 2) the phosphorylation/dephosphorylation of nuclear MLC20 results in the sliding of myosin and actin molecules past each other producing relative motion between the DNA bound to the myosin II and RNA polymerase II holoenzyme bound to actins and nucleoskeleton.
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