Phosphoproteomics Reveals the AMPK Substrate Network in Response to DNA Damage and Histone Acetylation

AMP-activated protein kinase (AMPK) is a conserved energy sensor that plays roles in diverse biological processes via phosphorylating various substrates. Emerging studies have demonstrated the regulatory roles of AMPK in DNA repair, but the underlying mechanisms remain to be fully understood. Herein...

Full description

Saved in:
Bibliographic Details
Published in:Genomics, proteomics & bioinformatics proteomics & bioinformatics, 2022-08, Vol.20 (4), p.597-613
Main Authors: Jiang, Yuejing, Cong, Xiaoji, Jiang, Shangwen, Dong, Ying, Zhao, Lei, Zang, Yi, Tan, Minjia, Li, Jia
Format: Article
Language:English
Subjects:
AMPK
Apoptosis
DNA damage
Histone modification
Original Research
Phosphoproteomics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:AMP-activated protein kinase (AMPK) is a conserved energy sensor that plays roles in diverse biological processes via phosphorylating various substrates. Emerging studies have demonstrated the regulatory roles of AMPK in DNA repair, but the underlying mechanisms remain to be fully understood. Herein, using mass spectrometry-based proteomic technologies, we systematically investigate the regulatory network of AMPK in DNA damage response (DDR). Our system-wide phosphoproteome study uncovers a variety of newly-identified potential substrates involved in diverse biological processes, whereas our system-wide histone modification analysis reveals a link between AMPK and histone acetylation. Together with these findings, we discover that AMPK promotes apoptosis by phosphorylating apoptosis-stimulating of p53 protein 2 (ASPP2) in an irradiation (IR)-dependent manner and regulates histone acetylation by phosphorylating histone deacetylase 9 (HDAC9) in an IR-independent manner. Besides, we reveal that disrupting the histone acetylation by the bromodomain BRD4 inhibitor JQ-1 enhances the sensitivity of AMPK-deficient cells to IR. Therefore, our study has provided a resource to investigate the interplay between phosphorylation and histone acetylation underlying the regulatory network of AMPK, which could be beneficial to understand the exact role of AMPK in DDR.
ISSN:1672-0229
2210-3244
DOI:10.1016/j.gpb.2020.09.003