Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Australian Regenerative Medicine Institute and Systems Biology Institute, Monash University, Clayton, VIC, Australia.
Nat Commun. 2021 Oct 8;12(1):5904. doi: 10.1038/s41467-021-26125-x.
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.
importin 超家族成员 Importin-13 是一种双向核转运蛋白。为了阐明其功能作用，我们对野生型和 Importin-13 敲除的小鼠胚胎干细胞进行了转录组分析，发现涉及应激反应和细胞凋亡调控的差异表达基因富集。对 277 个对氧化应激有反应的 Importin-13 依赖性基因的新启动子基序分析表明，富含与转录因子特异性蛋白 1（SP1）或 Kruppel 样因子 4（KLF4）的共识位点相对应的基序。对氧化应激下的胚胎干细胞进行分析发现，Importin-13 敲除细胞更具抗性，敲低 SP1 或 KLF4 有助于保护野生型胚胎干细胞免受应激诱导的死亡。在细胞环境中发现 Importin-13 与 SP1 和 KLF4 结合，在这两种转录因子依赖氧化应激的核输出中起关键作用。这些结果对于理解应激生物学至关重要，突出了 Importin-13 在应激反应中的重要性。
