Reversible acetylation modulates p54nrb/NONO-mediated expression of the interleukin 8 gene

Jae Eun Ryu, Taek Yeol Jung, Seong Hoon Park, Jun Hong Park, Hyun Seok Kim

Research output: Contribution to journalArticlepeer-review

Abstract

The non-POU domain-containing octamer-binding protein (NONO, also referred to as p54nrb) is a multifunctional nuclear protein engaging in transcriptional regulation, mRNA splicing, nuclear retention of defective RNA, and DNA repair. Emerging evidence has demonstrated that p54nrb is subjected to various posttranslational modifications, including phosphorylation and methylation, which may be important regulators of its multifunction. However, among these modifications, direct evidence of p54nrb acetylation and its underlying mechanism remains unclear. In this study, we reported that lysine 371 of p54nrb was reversibly acetylated by the acetyltransferase general control non-depressible 5 (GCN5) and deacetylase sirtuin 1 (SIRT1), which was crucial for activity of p54nrb to inhibit interleukin-8 (IL-8) expression. Mechanistically, GCN5-mediated acetylation attenuates the recruitment of p54nrb on its core binding motif within the IL-8 gene promoter, preferentially increasing the expression of the IL-8 gene. In contrast, deacetylation by SIRT1 reverses this process. Altogether, our data suggest that reversible acetylation is an important switch for the multiple nuclear functions of p54nrb/NONO.

Original languageEnglish
Pages (from-to)50-56
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume622
DOIs
StatePublished - 24 Sep 2022

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (2021R1F1A1048942, 2019R1A5A6099645, 2020R1A2C2003685, and 2019R1A2C1083823to H-S.K), the National Research Council of Science and Technology (1711149020 to S-H.P and JH.P), the Korea Institute of Toxicology (1711133843 to S-H.P), and the Ministry of Education (2019R1A6C1010020 to H-S.K).

Funding Information:
This work was supported by grants from the National Research Foundation of Korea ( 2021R1F1A1048942 , 2019R1A5A6099645 , 2020R1A2C2003685 , and 2019R1A2C1083823 to H-S.K), the National Research Council of Science and Technology ( 1711149020 to S-H.P and JH.P), the Korea Institute of Toxicology ( 1711133843 to S-H.P), and the Ministry of Education ( 2019R1A6C1010020 to H-S.K).

Publisher Copyright:
© 2022 The Authors

Keywords

  • General control non-depressible 5 (GCN5)
  • Interleukin-8 (IL-8)
  • Lysine acetylation
  • Sirtuin 1 (SIRT1)
  • p54nrb

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