Nuclear transporter Importin-13 plays a key role in the oxidative stress transcriptional response

K A Gajewska; H Lescesen; M Ramialison; K M Wagstaff; D A Jans

doi:10.1038/s41467-021-26125-x

Nuclear transporter Importin-13 plays a key role in the oxidative stress transcriptional response

Nat Commun. 2021 Oct 8;12(1):5904. doi: 10.1038/s41467-021-26125-x.

Authors

K A Gajewska¹, H Lescesen¹, M Ramialison², K M Wagstaff¹, D A Jans³

Affiliations

¹ Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
² Australian Regenerative Medicine Institute and Systems Biology Institute, Monash University, Clayton, VIC, Australia.
³ Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia. david.jans@monash.edu.

Abstract

The importin superfamily member Importin-13 is a bidirectional nuclear transporter. To delineate its functional roles, we performed transcriptomic analysis on wild-type and Importin-13-knockout mouse embryonic stem cells, revealing enrichment of differentially expressed genes involved in stress responses and apoptosis regulation. De novo promoter motif analysis on 277 Importin-13-dependent genes responsive to oxidative stress revealed an enrichment of motifs aligned to consensus sites for the transcription factors specificity protein 1, SP1, or Kruppel like factor 4, KLF4. Analysis of embryonic stem cells subjected to oxidative stress revealed that Importin-13-knockout cells were more resistant, with knockdown of SP1 or KLF4 helping protect wild-type embryonic stem cells against stress-induced death. Importin-13 was revealed to bind to SP1 and KLF4 in a cellular context, with a key role in oxidative stress-dependent nuclear export of both transcription factors. The results are integral to understanding stress biology, highlighting the importance of Importin-13 in the stress response.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Active Transport, Cell Nucleus / physiology*
Animals
Embryonic Stem Cells
HeLa Cells
Humans
Hydrogen Peroxide / metabolism
Karyopherins / genetics*
Karyopherins / metabolism*
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors / genetics
Kruppel-Like Transcription Factors / metabolism
Mice
Mice, Knockout
Oxidative Stress / physiology*
Protein Kinases / genetics
Protein Kinases / metabolism
Transcription Factors / metabolism
Transcriptome

Substances

KLF4 protein, human
Karyopherins
Klf4 protein, mouse
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors
Transcription Factors
importin 13 protein, mouse
Hydrogen Peroxide
Protein Kinases
Sp1 kinase