From the Departments of Medical Biology and.
Pharmacy, Faculty of Health Sciences, UiT-The Arctic University of Norway, N-9037 Tromsø, Norway.
J Biol Chem. 2018 Dec 7;293(49):18965-18976. doi: 10.1074/jbc.RA118.004473. Epub 2018 Oct 10.
The long noncoding RNA (lncRNA) (nuclear enriched abundant transcript 1) is the architectural component of nuclear paraspeckles, and it has recently gained considerable attention as it is abnormally expressed in pathological conditions such as cancer and neurodegenerative diseases. and paraspeckle formation are increased in cells upon exposure to a variety of environmental stressors and believed to play an important role in cell survival. The present study was undertaken to further investigate the role of in cellular stress response pathways. We show that is a novel target gene of heat shock transcription factor 1 (HSF1) and is up-regulated when the heat shock response pathway is activated by sulforaphane (SFN) or elevated temperature. HSF1 binds specifically to a newly identified conserved heat shock element in the promoter. In line with this, SFN induced the formation of -containing paraspeckles via an HSF1-dependent mechanism. HSF1 plays a key role in the cellular response to proteotoxic stress by promoting the expression of a series of genes, including those encoding molecular chaperones. We have found that the expression of HSP70, HSP90, and HSP27 is amplified and sustained during heat shock in -depleted cells compared with control cells, indicating that feeds back via an unknown mechanism to regulate HSF1 activity. This interrelationship is potentially significant in human diseases such as cancer and neurodegenerative disorders.
长链非编码 RNA(lncRNA)(核丰富转录物 1)是核斑的结构成分,最近因其在癌症和神经退行性疾病等病理条件下异常表达而受到广泛关注。并且在细胞暴露于各种环境应激源时,斑形成增加,据信在细胞存活中发挥重要作用。本研究旨在进一步研究在细胞应激反应途径中的作用。我们表明是热休克转录因子 1(HSF1)的新型靶基因,并且当热休克反应途径被萝卜硫素(SFN)或升高的温度激活时被上调。HSF1特异性结合到启动子中一个新鉴定的保守热休克元件。与此一致,SFN 通过 HSF1 依赖性机制诱导含有 -的斑的形成。HSF1 通过促进一系列基因的表达,包括编码分子伴侣的基因,在细胞对蛋白毒性应激的反应中起关键作用。我们发现与对照细胞相比,在 -耗尽的细胞中,HSP70、HSP90 和 HSP27 的表达在热休克期间被放大和维持,表明通过未知机制反馈来调节 HSF1 活性。这种相互关系在癌症和神经退行性疾病等人类疾病中可能具有重要意义。