View : 121 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 SuKang, Dong HoonLee, Da HyunBae, Soo Han
Ewha Authors
강동훈
SCOPUS Author ID
강동훈scopus
Issue Date
2015
Journal Title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN
0006-291XJCR Link1090-2104JCR Link
Citation
vol. 466, no. 3, pp. 499 - 504
Keywords
PF-4708671p70 ribosomal S6 kinase 1 (S6K1)p62AutophagyNuclear factor erythroid 2-related factor 2 (Nrf2)Kelch-like ECH-associated protein 1 (Keap1)
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Indexed
SCI; SCIE; SCOPUS WOS scopus
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


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE