XAF1 forms a positive feedback loop with IRF-1 to drive apoptotic stress response and suppress tumorigenesis
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jeong, Seong-In | - |
dc.contributor.author | Kim, Jung-Wook | - |
dc.contributor.author | Ko, Kyung-Phil | - |
dc.contributor.author | Ryu, Byung-Kyu | - |
dc.contributor.author | Lee, Min-Goo | - |
dc.contributor.author | Kim, Hyo-Jong | - |
dc.contributor.author | Chi, Sung-Gil | - |
dc.date.accessioned | 2021-09-02T08:53:37Z | - |
dc.date.available | 2021-09-02T08:53:37Z | - |
dc.date.created | 2021-06-16 | - |
dc.date.issued | 2018-07-24 | - |
dc.identifier.issn | 2041-4889 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/74313 | - |
dc.description.abstract | X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a proapoptotic tumor suppressor that is frequently inactivated in multiple human cancers. However, the molecular basis for the XAF1-mediated growth inhibition remains largely undefined. Here, we report that XAF1 forms a positive feedback loop with interferon regulatory factor-1 (IRF-1) and functions as a transcriptional coactivator of IRF-1 to suppress tumorigenesis. Under various stressful conditions, XAF1 transcription is activated by IRF-1, and elevated XAF1 stabilizes and activates IRF-1. Mechanistically, XAF1 binds to the multifunctional domain 2 of IRF-1 via the zinc finger domain 6, thereby hindering C-terminus of Hsc70-interacting protein (CHIP) interaction with and ubiquitination of IRF-1. Activation of the IRF-1-XAF1 loop greatly increases stressinduced apoptosis and decreases the invasive capability of tumor cells. Oncogenic Ras and growth factors interfere with the IRF-1-XAF1 interplay via Erk-mediated repression of XAF1 transcription. Furthermore, XAF1 enhances IRF-1mediated transcription of proapoptotic genes via the XAF1-IRF-1 complex formation on these target promoters. Meanwhile, XAF1 inhibits NF-.B-mediated tumor cell malignancy by reinforcing IRF-1 binding to a subset of coregulated promoters. Expression levels of IRF-1 and XAF1 correlate tightly in both cancer cell lines and primary tumors, and XAF1-induced tumor regression is markedly attenuated in IRF-1-depleted tumors. Collectively, this study identifies a novel mechanism of XAF1-mediated tumor suppression, uncovering XAF1 as a feedback coactivator of IRF1 under stressful conditions. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | REGULATORY FACTOR-I | - |
dc.subject | XIAP-ASSOCIATED FACTOR-1 | - |
dc.subject | X-LINKED INHIBITOR | - |
dc.subject | NF-KAPPA-B | - |
dc.subject | CANCER-CELLS | - |
dc.subject | GASTROINTESTINAL CANCER | - |
dc.subject | MEDIATES APOPTOSIS | - |
dc.subject | PROSTATE-CANCER | - |
dc.subject | UP-REGULATION | - |
dc.subject | COLON-CANCER | - |
dc.title | XAF1 forms a positive feedback loop with IRF-1 to drive apoptotic stress response and suppress tumorigenesis | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Min-Goo | - |
dc.contributor.affiliatedAuthor | Chi, Sung-Gil | - |
dc.identifier.doi | 10.1038/s41419-018-0867-4 | - |
dc.identifier.scopusid | 2-s2.0-85050645869 | - |
dc.identifier.wosid | 000440242200002 | - |
dc.identifier.bibliographicCitation | CELL DEATH & DISEASE, v.9 | - |
dc.relation.isPartOf | CELL DEATH & DISEASE | - |
dc.citation.title | CELL DEATH & DISEASE | - |
dc.citation.volume | 9 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | REGULATORY FACTOR-I | - |
dc.subject.keywordPlus | XIAP-ASSOCIATED FACTOR-1 | - |
dc.subject.keywordPlus | X-LINKED INHIBITOR | - |
dc.subject.keywordPlus | NF-KAPPA-B | - |
dc.subject.keywordPlus | CANCER-CELLS | - |
dc.subject.keywordPlus | GASTROINTESTINAL CANCER | - |
dc.subject.keywordPlus | MEDIATES APOPTOSIS | - |
dc.subject.keywordPlus | PROSTATE-CANCER | - |
dc.subject.keywordPlus | UP-REGULATION | - |
dc.subject.keywordPlus | COLON-CANCER | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(02841) 서울특별시 성북구 안암로 14502-3290-1114
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.