Nuclear import of IER5 is mediated by a classical bipartite nuclear localization signal and is required for HSF1 full activation

Exp Cell Res. 2020 Jan 1;386(1):111686. doi: 10.1016/j.yexcr.2019.111686. Epub 2019 Nov 6.

Abstract

IER5 gene encodes an activator of HSF1 and is a p53 target gene. The IER5 protein forms a ternary complex with HSF1 and PP2A, and promotes PP2A-dependent dephosphorylation of HSF1 at a number of serine and threonine residues. This hypo-phosphorylated form of HSF1 is transcriptionally active and has been suggested to be responsible for the HSF1 activation observed in cancers. Here we report that IER5 possess a classical bipartite nuclear localization signal (NLS) at amino acids 217-244 that is highly conserved among species and that mediates complex formation with importin-α and importin-β. We also demonstrate that the intact NLS is essential for HSF1 dephosphorylation and full activation by IER5. Thus, nuclear import of IER5 via importin-α and importin-β may be essential for IER5 function.

Keywords: Cancer; HSF1; IER5; Importin; Nuclear localization signal; PP2A; Post-translational modification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Cell Line, Tumor
  • Cell Nucleus / metabolism*
  • Conserved Sequence
  • HEK293 Cells
  • Heat Shock Transcription Factors / metabolism
  • Humans
  • Immediate-Early Proteins / chemistry
  • Immediate-Early Proteins / metabolism*
  • Karyopherins / metabolism
  • Nuclear Localization Signals*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Phosphorylation

Substances

  • HSF1 protein, human
  • Heat Shock Transcription Factors
  • IER5 protein, human
  • Immediate-Early Proteins
  • Karyopherins
  • Nuclear Localization Signals
  • Nuclear Proteins