Spliced or Unspliced, That Is the Question: The Biological Roles of XBP1 Isoforms in Pathophysiology.
Spliced or Unspliced, That Is the Question: The Biological Roles of XBP1 Isoforms in Pathophysiology.
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剪接还是未剪接，这就是问题：XBP1 同工型在病理生理学中的生物学作用
DOI：
10.3390/ijms23052746
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发表时间：
2022-03-02
影响因子：
5.6
通讯作者：
Kasim V
中科院分区：
文献类型：
--
作者：
Luo X;Alfason L;Wei M;Wu S;Kasim V
X-box结合蛋白1 （XBP1）是CREB/ATF碱基区亮氨酸拉链家族的成员，转录为未剪接异构体（XBP1-u），在内质网应激下，被剪接成其剪接异构体（XBP1-s）。XBP1-s与主要组织相容性复合体II类基因的cAMP反应元件相互作用，通过调控未折叠蛋白反应（UPR）相关基因的转录活性，在未折叠蛋白反应（UPR）中发挥关键作用。XBP1-s还参与其他生理途径，包括脂质代谢、胰岛素代谢、免疫细胞分化。其异常表达与炎症、神经退行性疾病、病毒感染密切相关，对促进肿瘤进展和耐药至关重要。同时，最近的研究报道，XBP1-u的功能被低估了，因为它不仅仅是XBP1-s的前体。相反，XBP-1u是通过翻译后调控参与包括自噬和肿瘤发生在内的多种生物学途径的关键因子。本文就XBP1-u和XBP1-s的生物学功能及其与疾病的关系进行综述。
X-box binding protein 1 (XBP1) is a member of the CREB/ATF basic region leucine zipper family transcribed as the unspliced isoform (XBP1-u), which, upon exposure to endoplasmic reticulum stress, is spliced into its spliced isoform (XBP1-s). XBP1-s interacts with the cAMP response element of major histocompatibility complex class II gene and plays critical role in unfolded protein response (UPR) by regulating the transcriptional activity of genes involved in UPR. XBP1-s is also involved in other physiological pathways, including lipid metabolism, insulin metabolism, and differentiation of immune cells. Its aberrant expression is closely related to inflammation, neurodegenerative disease, viral infection, and is crucial for promoting tumor progression and drug resistance. Meanwhile, recent studies reported that the function of XBP1-u has been underestimated, as it is not merely a precursor of XBP1-s. Instead, XBP-1u is a critical factor involved in various biological pathways including autophagy and tumorigenesis through post-translational regulation. Herein, we summarize recent research on the biological functions of both XBP1-u and XBP1-s, as well as their relation to diseases.
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