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

Joo Weon Lim, Kyung Hwan Kim, Hyeyoung Kim

Research output: Contribution to journalArticle

16 Citations (Scopus)

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-α. 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-α 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-α and inhibits nuclear translocation of Ku70. Since NF-κB p65 activation induced the decrease of Hsc70 level, the interaction of Ku70 with importin-α and nuclear translocation of Ku70 increased upon the activation of NF-κB p65. NF-κB 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-κB p65, nuclear translocation of Ku70 increased through NF-κB p65-mediated decrease of Hsc70 level. The results suggest that the involvement of NF-κB 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.

Original languageEnglish
Pages (from-to)2065-2077
Number of pages13
JournalInternational Journal of Biochemistry and Cell Biology
Volume40
Issue number10
DOIs
Publication statusPublished - 2008 Mar 10

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology

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