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PreprintCited by 28Redox biology and oxidative stressUbiquitin and proteasome pathwaysCancer-related gene regulation

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Acetylation-dependent coupling between G6PD activity and apoptotic signaling

Open access
Wu, Fang, Muskat, Natali H., Dvilansky, Inbar, Koren, Omri, Shahar, Anat, Gazit, Roi, Elia, Natalie, Arbely, Eyal·2023·Nature Communications
DOI 10.1101/2023.02.19.529048PMC PMC10556143

Preprint — published as 10.1038/s41467-023-41895-2

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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

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Metadata

Authors
Wu, F., Muskat, N. H., Dvilansky, I., Koren, O., Shahar, A., Gazit, R., Elia, N., & Arbely, E.
Affiliations
Ben-Gurion University of the Negev (IL)
Corresponding author
Arbely, Eyal
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2023-02-19
Volume
14
Issue
1
Pages
6208-6208
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/2023.02.19.529048
PMC
PMC10556143
OpenAlex
W4387372445
Cited by
28
References
1
Citations by year
2026: 8 · 2025: 16 · 2024: 4
FWCI
2.49
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • European Commission (HORIZON2020)
  • Israel Science Foundation (678461)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
Keywords
lysine acetylation, glucose-6-phosphate dehydrogenase, pentose phosphate pathway, enzyme regulation, post-translational modification, ubiquitination, p53, apoptosis, protein dimer structure, phosphorylation, metabolic signaling
MeSH terms
Acetylation, Humans, Lysine, Protein Processing, Post-Translational

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