Septin 9 isoform 1 (SEPT9_i1) specifically interacts with importin-α7 to drive hypoxia-inducible factor (HIF)-1α nuclear translocation

Keren Tazat, Susanne Schindler, Reinhard Depping, Nicola J. Mabjeesh

Research output: Contribution to journalArticlepeer-review

Abstract

We have shown previously that septin 9 isoform 1 (SEPT9_i1) protein associates with hypoxia-inducible factor (HIF)-1α to augment HIF-1 transcriptional activity by driving its importin-α-mediated nuclear translocation. Using in vitro and in vivo binding assays we identified that HIF-1α interacts with importin-α5 and importin-α7 in prostate cancer cells but only importin-α7 interacts with SEPT9_i1. The interaction with importin-α7 was dependent on the first 25 amino acids of SEPT9_i1 that are unique compared to other members of the mammalian septin family. Depletion of endogenous importin-α7 reduced HIF-1α levels in the nucleus. Our results provide evidence that there are importin-α specificities in the cytosolic/nuclear translocation process of HIF-1α protein, which may act differently under certain pathophysiological circumstances where SEPT9_i1 is overexpressed.

Original languageEnglish
Pages (from-to)123-130
Number of pages8
JournalCytoskeleton
Volume76
Issue number1
DOIs
StatePublished - Jan 2019

Keywords

  • HIF-1α
  • SEPT9_i1
  • cancer
  • importin-α7
  • translocation

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