SUMO modification regulates the transcriptional activity of XBP1

被引：54

作者：

Chen, Hui ^{[1
]}

Qi, Ling ^{[1
]}

机构：

[1] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA

来源：

BIOCHEMICAL JOURNAL | 2010年 / 429卷

关键词：

post-translational modification; protein inhibitor of activated signal transducer and activator of transcription (PIAS); small ubiquitin-related modifier (SUMO); transcriptional regulation; unfolded protein response (UPR); X-box-binding protein 1 (XBP1); UNFOLDED PROTEIN RESPONSE; PLASMA-CELL DIFFERENTIATION; MESSENGER-RNA; ER STRESS; TRANSMEMBRANE PROTEIN; REPRESSION; REQUIRES; KINASE; SUMOYLATION; DISEASE;

D O I：

10.1042/BJ20100193

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The UPR (unfolded protein response), a cellular defence mechanism against misfolded protein accumulation in the ER (endoplasmic reticulum), is associated with many human diseases such as aging, cancer and diabetes. XBP1 (X-box-binding protein 1), a key transcription factor of the UPR, is critical in maintaining ER homoeostasis. Nevertheless, the mechanism by which XBP1 transcriptional activity is regulated remains unexplored. In the present study we show that XBP1s, the active spliced form of XBP1 protein, is SUMOylated, mainly by PIAS2 [protein inhibitor of activated STAT (signal transducer and activator of transcription) 2] at two lysine residues located in 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 an unexpected role for SUMO (small ubiquitin-related modifier) in the regulation of UPR activation and ER homoeostasis.

引用

页码：95 / 102

页数：8

共 35 条

[11] XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease [J].