Novel properties of the protein kinase CK2-site-regulated nuclear-localization sequence of the interferon-induced nuclear factor IFI 16

L. J. Briggs, R. W. Johnstone, R. M. Elliot, C. Y. Xiao, M. Dawson, J. A. Trapani, D. A. Jans

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Abstract

Members of the interferon-induced class of nuclear factors possess a putative CcN motif, comparable with that within proteins such as the simian virus 40 large tumour antigen (T-ag), which confers phosphorylation-mediated regulation of nuclear-localization sequence (NLS)-dependent nuclear import. Here we examine the functionality of the interferon-induced factor 16 (IFI 16) CcN motif, demonstrating its ability to target a heterologous protein to the nucleus, and to be phosphorylated specifically by the CcN-motif-phosphorylating protein kinase CK2 (CK2). The IFI 16 NLS, however, has novel properties, conferring ATP-dependent nuclear import completely independent of cytosolic factors, as well as binding to nuclear components. The IFI 16 NLS is not recognized with high affinity by the NLS-binding importin heterodimer, and transport mediated by it is insensitive to non-hydrolysable GTP analogues. The IFI 16 NLS thus mediates nuclear import through a pathway completely distinct from that of conventional NLSs, such as that of T-ag, but intriguingly resembling that of the NLS of the HIV-1 transactivator protein Tat. Since the IFI 16 CK2 site enhances nuclear import through facilitating binding to nuclear components, this represents a novel mechanism by which the site regulates nuclear-protein import, and constitutes a difference between the IFI 16 and Tat NLSs that may be of importance in the immune response.

Original languageEnglish
Pages (from-to)69-77
Number of pages9
JournalBiochemical Journal
Volume353
Issue number1
DOIs
Publication statusPublished - 1 Jan 2001
Externally publishedYes

Keywords

  • Myeloid cell
  • Nuclear transport
  • Phosphorylation
  • Protein kinase
  • Transcription factor

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