期刊
BIOCHEMICAL JOURNAL
卷 429, 期 -, 页码 95-102出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20100193
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)
资金
- American Federation for Aging Research [RAG08061]
- National Institute of Diabetes and Digestive and Kidney Disease [R01DK082582]
- Rosalinde and Arthur Foundation/American Federation for Aging Research
- American Diabetes Association (ADA)
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.
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