SUMO modification regulates the transcriptional activity of XBP1.
SUMO modification regulates the transcriptional activity of XBP1.
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DOI：
10.1042/bj20100193
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发表时间：
2010-07-01
期刊：
影响因子：
--
通讯作者：
Qi L
中科院分区：
文献类型：
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作者：
Chen H;Qi L
未折叠蛋白反应（unfolded protein response，UPR）是一种针对内质网（endoplasmic reticulum，ER）中错误折叠蛋白积聚的细胞防御机制，与许多人类疾病如衰老、癌症和糖尿病相关。X-box结合蛋白1（X-box binding protein 1，XBP 1）是UPR的关键转录因子，在维持内质网稳态中起重要作用。尽管如此，调节XBP 1转录活性的机制仍未被探索。在这里，我们表明，XBP 1蛋白的活性形式，XBP 1 s，是SUMO化主要由激活的STAT 2（PIAS 2）的蛋白抑制剂在两个赖氨酸残基位于C-末端的反式激活结构域。这些SUMO化事件的消除显著增强了XBP 1对UPR靶基因的转录活性。因此，我们的研究结果揭示了SUMO在调节UPR激活和ER稳态中的一个先前意想不到的作用。
The unfolded protein response (UPR), a cellular defense mechanism against misfolded protein accumulation in the endoplasmic reticulum (ER), is associated with many human diseases such as aging, cancer and diabetes. X-box binding protein 1 (XBP1), a key transcription factor of the UPR, is critical in maintaining ER homeostasis. Nonetheless, the mechanism by which XBP1 transcriptional activity is regulated remains unexplored. Here we show that the active form of XBP1 protein, XBP1s, is SUMOylated mainly by the protein inhibitors of activated STAT 2 (PIAS2) at two lysine residues located at the C-terminal transactivation domain. Ablation of these SUMOylation events significantly enhances the transcriptional activity of XBP1s towards UPR target genes. Thus, our results reveal a previously unexpected role for SUMO in the regulation of UPR activation and ER homeostasis.