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http://ir.nhri.org.tw/handle/3990099045/8401
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| Title: | GCN5 inhibits XBP-1S-mediated transcription by antagonizing PCAF action |
| Authors: | Lew, QJ;Chu, KL;Chia, YL;Soo, B;Ho, JP;Ng, CH;Kwok, HS;Chiang, CM;Chang, Y;Chao, SH |
| Contributors: | Division of Infectious Diseases |
| Abstract: | Cellular unfolded protein response (UPR) is induced when endoplasmic reticulum (ER) is under stress. XBP-1S, the active isoform of X-box binding protein 1 (XBP-1), is a key regulator of UPR. Previously, we showed that a histone acetyltransferase (HAT), p300/CBP-associated factor (PCAF), binds to XBP-1S and functions as an activator of XBP-1S. Here, we identify general control nonderepressible 5 (GCN5), a HAT with 73% identity to PCAF, as a novel XBP-1S regulator. Both PCAF and GCN5 bind to the same domain of XBP-1S. Surprisingly, GCN5 potently blocks the XBP-1S-mediated transcription, including cellular UPR genes and latent membrane protein 1 of Epstein-Barr virus. Unlike PCAF, GCN5 acetylates XBP-1S and enhances nuclear retention and protein stability of XBP-1S. However, such GCN5-mediated acetylation of XBP-1S shows no effects on XBP-1S activity. In addition, the HAT activity of GCN5 is not required for repression of XBP-1S target genes. We further demonstrate that GCN5 inhibits XBP-1S-mediated transcription by disrupting the PCAF-XBP-1S interaction and preventing the recruitment of XBP-1S to its target genes. Taken together, our results represent the first work demonstrating that GCN5 and PCAF exhibit different functions and antagonistically regulate the XBP-1S-mediated transcription. |
| Date: | 2015-01 |
| Relation: | Oncotarget. 2015 Jan;6(1):271-287. |
| Link to: | http://dx.doi.org/10.18632/oncotarget.2773 |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000352065200023 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84921405901 |
| Appears in Collections: | [張堯] 期刊論文
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| PUB25426559.pdf | | 1186Kb | Adobe PDF | 519 | View/Open |
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