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胃癌细胞和胰腺腺泡细胞中的DNA修复Ku蛋白

DNA repair Ku proteins in gastric cancer cells and pancreatic acinar cells.

作者信息

Kim H

机构信息

Department of Food and Nutrition, Brain Korea 21 Project, College of Human Ecology and Biomolecule Secretion Research Center, Institute of Gastroenterology, College of Medicine, Yonsei University, Seoul, Korea.

出版信息

Amino Acids. 2008 Feb;34(2):195-202. doi: 10.1007/s00726-006-0411-1. Epub 2006 Oct 12.

Abstract

The DNA repair protein Ku acts as a heterodimer of Ku70 and Ku80 that binds to the DNA ends, nicks, or single-to-double-strand transition. It has a crucial role for DNA double-strand-break repair. Either Ku70 or Ku80 itself may have a unique function that is independent of the other Ku subunit. In this review, the role of Ku on cell proliferation and apoptosis will be discussed. Ku acts as a regulator of transcription by interacting with the recombination signal binding protein Jkappa and the NF-kappaB p50 homodimer to up-regulate p50 expression, which may regulate the proliferation of gastric cancer cells. Both Ku70 and Ku80 expressions are mediated by constitutively activated NF-kappaB and constitutively expressed cyclooxygenase-2 in gastric cancer cells, which may be related to gastric cell proliferation and carcinogenesis. In addition, nuclear loss of Ku may underlie the mechanism of apoptosis in pancreatic acinar cells after oxidative stress.

摘要

DNA修复蛋白Ku以Ku70和Ku80的异二聚体形式存在,它能与DNA末端、切口或单链到双链的转变部位结合。它在DNA双链断裂修复中起关键作用。Ku70或Ku80自身可能具有独立于另一个Ku亚基的独特功能。在本综述中,将讨论Ku在细胞增殖和凋亡中的作用。Ku通过与重组信号结合蛋白Jkappa和NF-κB p50同二聚体相互作用来上调p50表达,从而作为转录调节因子,这可能调节胃癌细胞的增殖。在胃癌细胞中,Ku70和Ku80的表达均由组成性激活的NF-κB和组成性表达的环氧化酶-2介导,这可能与胃细胞增殖和致癌作用有关。此外,Ku的核丢失可能是氧化应激后胰腺腺泡细胞凋亡机制的基础。

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