Acetylation-dependent coupling between G6PD activity and apoptotic signaling

Fang Wu, Natali H. Muskat, Inbar Dvilansky, Omri Koren, Anat Shahar, Roi Gazit, Natalie Elia and Eyal Arbely ()
Additional contact information
Fang Wu: Ben-Gurion University of the Negev
Natali H. Muskat: Ben-Gurion University of the Negev
Inbar Dvilansky: Ben-Gurion University of the Negev
Omri Koren: Ben-Gurion University of the Negev
Anat Shahar: Ben-Gurion University of the Negev
Roi Gazit: Ben-Gurion University of the Negev
Natalie Elia: Ben-Gurion University of the Negev
Eyal Arbely: Ben-Gurion University of the Negev

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Lysine acetylation has been discovered in thousands of non-histone human proteins, including most metabolic enzymes. Deciphering the functions of acetylation is key to understanding how metabolic cues mediate metabolic enzyme regulation and cellular signaling. Glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway, is acetylated on multiple lysine residues. Using site-specifically acetylated G6PD, we show that acetylation can activate (AcK89) and inhibit (AcK403) G6PD. Acetylation-dependent inactivation is explained by structural studies showing distortion of the dimeric structure and active site of G6PD. We provide evidence for acetylation-dependent K95/97 ubiquitylation of G6PD and Y503 phosphorylation, as well as interaction with p53 and induction of early apoptotic events. Notably, we found that the acetylation of a single lysine residue coordinates diverse acetylation-dependent processes. Our data provide an example of the complex roles of acetylation as a posttranslational modification that orchestrates the regulation of enzymatic activity, posttranslational modifications, and apoptotic signaling.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-41895-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41895-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-41895-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().