核因子-κB p65通过降解胰腺腺泡AR42J细胞中的热休克同源蛋白70来调节Ku70的核转位。

NF-kappaB p65 regulates nuclear translocation of Ku70 via degradation of heat shock cognate protein 70 in pancreatic acinar AR42J cells.

作者信息

Lim Joo Weon, Kim Kyung Hwan, Kim Hyeyoung

机构信息

Institute of Gastroenterology, Brain Korea 21 Project for Medical Science, College of Medicine, Yonsei University, Seoul 120-752, Republic of Korea.

出版信息

Int J Biochem Cell Biol. 2008;40(10):2065-77. doi: 10.1016/j.biocel.2008.02.015. Epub 2008 Mar 10.

DOI:10.1016/j.biocel.2008.02.015

Abstract

Ku proteins such as Ku70 and Ku80 play key roles in multiple nuclear processes. Nuclear translocation of Ku70 is independent of Ku80 translocation and mediated by nuclear localization signal (NLS) receptors including importin-alpha. In the present study using pancreatic acinar AR42J cells, heat shock cognate protein 70 (Hsc70) was identified as the protein associated with NLS of Ku70. Interaction of Ku70 with importin-alpha and nuclear translocation of Ku70 was suppressed by overexpression of Hsc70, but enhanced by downregulation of Hsc70. The results suggest that the formation of Ku70 complex with Hsc70 prevents NLS of Ku70 from access of importin-alpha and inhibits nuclear translocation of Ku70. Since NF-kappaB p65 activation induced the decrease of Hsc70 level, the interaction of Ku70 with importin-alpha and nuclear translocation of Ku70 increased upon the activation of NF-kappaB p65. NF-kappaB p65 induced cell proliferation through decrease of Hsc70 levels and increase of nuclear translocation of Ku70. In the cells treated with cerulein as a physiological stimulus to activate NF-kappaB p65, nuclear translocation of Ku70 increased through NF-kappaB p65-mediated decrease of Hsc70 level. The results suggest that the involvement of NF-kappaB p65 in nuclear translocation of Ku70 may be mediated by Hsc70 degradation, which may play a key role in cell proliferation of pancreatic acinar AR42J cells.

摘要

诸如Ku70和Ku80之类的Ku蛋白在多种核过程中发挥关键作用。Ku70的核转位独立于Ku80的转位，并由包括输入蛋白α在内的核定位信号（NLS）受体介导。在本研究中，使用胰腺腺泡AR42J细胞，热休克同源蛋白70（Hsc70）被鉴定为与Ku70的NLS相关的蛋白。Hsc70的过表达抑制了Ku70与输入蛋白α的相互作用以及Ku70的核转位，但Hsc70的下调则增强了这种相互作用。结果表明，Ku70与Hsc70形成复合物可阻止Ku70的NLS与输入蛋白α结合，并抑制Ku70的核转位。由于NF-κB p65激活导致Hsc70水平降低，因此在NF-κB p65激活后，Ku70与输入蛋白α的相互作用以及Ku70的核转位增加。NF-κB p65通过降低Hsc70水平和增加Ku70的核转位来诱导细胞增殖。在用雨蛙肽作为激活NF-κB p65的生理刺激物处理的细胞中，Ku70的核转位通过NF-κB p65介导的Hsc70水平降低而增加。结果表明，NF-κB p65参与Ku70的核转位可能是由Hsc70降解介导的，这可能在胰腺腺泡AR42J细胞的增殖中起关键作用。