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Septin 9 isoform 1 (SEPT9_i1) specifically interacts with importin‐α7 to drive hypoxia‐inducible factor (HIF)‐1α nuclear translocation
Author(s) -
Tazat Keren,
Schindler Susanne,
Depping Reinhard,
Mabjeesh Nicola J.
Publication year - 2019
Publication title -
cytoskeleton
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.95
H-Index - 86
eISSN - 1949-3592
pISSN - 1949-3584
DOI - 10.1002/cm.21450
Subject(s) - importin , biology , microbiology and biotechnology , chromosomal translocation , nuclear localization sequence , nuclear protein , nuclear transport , cell nucleus , transcription factor , cytoplasm , biochemistry , gene
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.