View : 1370 Download: 0
PF-4708671, a specific inhibitor of p70 ribosomal S6 kinase 1, activates Nrf2 by promoting p62-dependent autophagic degradation of Keap1
- Title
- PF-4708671, a specific inhibitor of p70 ribosomal S6 kinase 1, activates Nrf2 by promoting p62-dependent autophagic degradation of Keap1
- Authors
- Park, Jeong Su; Kang, Dong Hoon; Lee, Da Hyun; Bae, Soo Han
- Ewha Authors
- 강동훈
- SCOPUS Author ID
- 강동훈
- Issue Date
- 2015
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- ISSN
- 0006-291X
1090-2104
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS vol. 466, no. 3, pp. 499 - 504
- Keywords
- PF-4708671; p70 ribosomal S6 kinase 1 (S6K1); p62; Autophagy; Nuclear factor erythroid 2-related factor 2 (Nrf2); Kelch-like ECH-associated protein 1 (Keap1)
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- Abstract
- p70 ribosomal S6 kinase 1 (S6K1) is an important serine/threonine kinase and downstream target of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. PF-4708671 is a specific inhibitor of S6K1, and prevents S6K1-mediated phosphorylation of the S6 protein. PF-4708671 treatment often leads to apoptotic cell death. However, the protective mechanism against PF-4708671-induced cell death has not been elucidated. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is essential for protecting cells against oxidative stress. p62, an adaptor protein in the autophagic process, enhances Nrf2 activation through the impairment of Keap1 activity. In this study, we showed that PF-4708671 induces autophagic Keap1 degradation-mediated Nrf2 activation in p62-dependent manner. Furthermore, p62-dependent Nrf2 activation plays a crucial role in protecting cells from PF-4708671-mediated apoptosis. (C) 2015 Elsevier Inc. All rights reserved.
- DOI
- 10.1016/j.bbrc.2015.09.059
- Appears in Collections:
- 연구기관 > 세포항상성연구센터 > Journal papers
- Files in This Item:
There are no files associated with this item.
- Export
- RIS (EndNote)
- XLS (Excel)
- XML