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

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.

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