Molecular mechanisms and functions of protein acetylation in sepsis and sepsis-associated organ dysfunction

Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA J Am Med Assoc. 2016;315(8):801–10.

CAS  Google Scholar 

Purcarea A, Sovaila S. Sepsis, a 2020 review for the internist. Rom J Intern Med. 2020;58(3):129–37.

Google Scholar 

Vincent JL, Marshall JC, Namendys-Silva SA, Francois B, Martin-Loeches I, Lipman J, et al. Assessment of the worldwide burden of critical illness: the intensive care over nations (ICON) audit. Lancet Resp Med. 2014;2(5):380–6.

Google Scholar 

Hattori Y, Hattori K, Suzuki T, Matsuda N. Recent advances in the pathophysiology and molecular basis of sepsis-associated organ dysfunction: novel therapeutic implications and challenges. Pharmacol Therapeut. 2017;177:56–66.

CAS  Google Scholar 

van der Poll T, van de Veerdonk FL, Scicluna BP, Netea MG. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol. 2017;17(7):407–20.

Google Scholar 

Huang M, Cai S, Su J. The pathogenesis of sepsis and potential therapeutic targets. Int J Mol Sci. 2019. https://doi.org/10.3390/ijms20215376.

Google Scholar 

Hotchkiss RS, Tinsley KW, Swanson PE, Karl IE. Endothelial cell apoptosis in sepsis. Crit Care Med. 2002;30(5 Suppl):S225–8.

Google Scholar 

Gotts JE, Matthay MA. Sepsis: pathophysiology and clinical management. Bmj-Brit Med J. 2016;353: i1585.

Google Scholar 

Lee JM, Hammaren HM, Savitski MM, Baek SH. Control of protein stability by post-translational modifications. Nat Commun. 2023;14(1):201.

CAS  Google Scholar 

Salovska B, Liu Y. Post-translational modification and phenotype. Proteomics. 2023;23(3–4): e2200535.

Google Scholar 

Jiang N, Li W, Jiang S, Xie M, Liu R. Acetylation in pathogenesis: revealing emerging mechanisms and therapeutic prospects. Biomed Pharmacother. 2023;167: 115519.

CAS  Google Scholar 

Yang K, Fan M, Wang X, Xu J, Wang Y, Tu F, et al. Lactate promotes macrophage HMGB1 lactylation, acetylation, and exosomal release in polymicrobial sepsis. Cell Death Differ. 2022;29(1):133–46.

CAS  Google Scholar 

Shang S, Liu J, Hua F. Protein acylation: mechanisms, biological functions and therapeutic targets. Signal Transduct Tar. 2022;7(1):396.

CAS  Google Scholar 

Allfrey VG, Faulkner R, Mirsky AE. Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc Natl Acad Sci USA. 1964;51(5):786–94.

CAS  Google Scholar 

Phillips DM. The presence of acetyl groups of histones. Biochem J. 1963;87(2):258–63.

CAS  Google Scholar 

Verdin E, Ott M. 50 years of protein acetylation: from gene regulation to epigenetics, metabolism and beyond. Nat Rev Mol Cell Biol. 2015;16(4):258–64.

CAS  Google Scholar 

Gu W, Roeder RG. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell. 1997;90(4):595–606.

CAS  Google Scholar 

Li P, Ge J, Li H. Lysine acetyltransferases and lysine deacetylases as targets for cardiovascular disease. Nat Rev Cardiol. 2020;17(2):96–115.

CAS  Google Scholar 

Wang P, Wang Z, Liu J. Role of HDACs in normal and malignant hematopoiesis. Mol Cancer. 2020;19(1):5.

Google Scholar 

Wu QJ, Zhang TN, Chen HH, Yu XF, Lv JL, Liu YY, et al. The sirtuin family in health and disease. Signal Transduct Tar. 2022;7(1):402.

CAS  Google Scholar 

Dang F, Wei W. Targeting the acetylation signaling pathway in cancer therapy. Semin Cancer Biol. 2022;85:209–18.

CAS  Google Scholar 

Lai W, Pugh BF. Understanding nucleosome dynamics and their links to gene expression and DNA replication. Nat Rev Mol Cell Bio. 2017;18(9):548–62.

CAS  Google Scholar 

Millan-Zambrano G, Burton A, Bannister AJ, Schneider R. Histone post-translational modifications – cause and consequence of genome function. Nat Rev Genet. 2022;23(9):563–80.

CAS  Google Scholar 

Di Cerbo V, Mohn F, Ryan DP, Montellier E, Kacem S, Tropberger P, et al. Acetylation of histone H3 at lysine 64 regulates nucleosome dynamics and facilitates transcription. Elife. 2014;3: e01632.

Google Scholar 

Geffen Y, Anand S, Akiyama Y, Yaron TM, Song Y, Johnson JL, et al. Pan-cancer analysis of post-translational modifications reveals shared patterns of protein regulation. Cell. 2023;186(18):3945-3967.e26.

CAS  Google Scholar 

Wang L, Yang X, Zhao K, Huang S, Qin Y, Chen Z, et al. MOF-mediated acetylation of UHRF1 enhances UHRF1 E3 ligase activity to facilitate DNA methylation maintenance. Cell Rep. 2024;43(3): 113908.

CAS  Google Scholar 

Wu F, Muskat NH, Dvilansky I, Koren O, Shahar A, Gazit R, et al. Acetylation-dependent coupling between G6PD activity and apoptotic signaling. Nat Commun. 2023;14(1):6208.

CAS  Google Scholar 

Nihira NT, Ogura K, Shimizu K, North BJ, Zhang J, Gao D, et al. Acetylation-dependent regulation of MDM2 E3 ligase activity dictates its oncogenic function. Sci Signal. 2017. https://doi.org/10.1126/scisignal.aai8026.

Google Scholar 

Lin H, Cheng K, Kubota H, Lan Y, Riedel SS, Kakiuchi K, et al. Histone methyltransferase DOT1L is essential for self-renewal of germline stem cells. Gene Dev. 2022;36(11–12):752–63.

CAS  Google Scholar 

Liu C, Yang Q, Zhu Q, Lu X, Li M, Hou T, et al. CBP mediated DOT1L acetylation confers DOT1L stability and promotes cancer metastasis. Theranostics. 2020;10(4):1758–76.

CAS  Google Scholar 

Liu Y, Xun W, Zhao T, Huang M, Sun L, Wen G, et al. Interplay between acetylation and ubiquitination controls PSAT1 protein stability in lung adenocarcinoma. Commun Biol. 2024;7(1):1365.

CAS  Google Scholar 

Yu P, Han Y, Meng L, Tang Z, Jin Z, Zhang Z, et al. The incorporation of acetylated LAP-TGF-beta1 proteins into exosomes promotes TNBC cell dissemination in lung micro-metastasis. Mol Cancer. 2024;23(1):82.

CAS  Google Scholar 

Gao Y, Nihira NT, Bu X, Chu C, Zhang J, Kolodziejczyk A, et al. Acetylation-dependent regulation of PD-L1 nuclear translocation dictates the efficacy of anti-PD-1 immunotherapy. Nat Cell Biol. 2020;22(9):1064–75.

CAS  Google Scholar 

Gao B, Wang Z, Dai K, Wang Y, Li L, Li G, et al. Acetylation of mtHSP70 at Lys595/653 affecting its interaction between GrpEL1 regulates glioblastoma progression via UPRmt. Free Radical Bio Med. 2024;213:394–408.

CAS  Google Scholar 

Luo J, Li M, Tang Y, Laszkowska M, Roeder RG, Gu W. Acetylation of p53 augments its site-specific DNA binding both in vitro and in vivo. Proc Natl Acad Sci USA. 2004;101(8):2259–64.

CAS  Google Scholar 

Garcia MJ, Hans F, von Zweydorf F, Feederle R, Elsasser SJ, Skodras AA, et al. Sirtuin-1 sensitive lysine-136 acetylation drives phase separation and pathological aggregation of TDP-43. Nat Commun. 2022;13(1):1223.

Google Scholar 

Matsuzaki H, Daitoku H, Hatta M, Aoyama H, Yoshimochi K, Fukamizu A. Acetylation of Foxo1 alters its DNA-binding ability and sensitivity to phosphorylation. P Natl Acad Sci Usa. 2005;102(32):11278–83.

CAS  Google Scholar 

Jin J, Zhang L, Li X, Xu W, Yang S, Song J, et al. Oxidative stress-CBP axis modulates MOB1 acetylation and activates the Hippo signaling pathway. Nucleic Acids Res. 2022;50(7):3817–34.

CAS  Google Scholar 

Yi F, Zhang Y, Wang Z, Wang Z, Li Z, Zhou T, et al. The deacetylation-phosphorylation regulation of SIRT2-SMC1A axis as a mechanism of antimitotic catastrophe in early tumorigenesis. Sci Adv. 2021. https://doi.org/10.1126/sciadv.abe5518.

Google Scholar 

Zhu Y, Gu L, Lin X, Liu C, Lu B, Cui K, et al. Dynamic regulation of ME1 phosphorylation and acetylation affects lipid metabolism and colorectal tumorigenesis. Mol Cell. 2020;77(1):138-149.e5.

CAS  Google Scholar 

Lei MZ, Li XX, Zhang Y, Li JT, Zhang F, Wang YP, et al. Acetylation promotes BCAT2 degradation to suppress BCAA catabolism and pancreatic cancer growth. Signal Transduct Tar. 2020;5(1):70.

CAS  Google Scholar 

You Z, Jiang WX, Qin LY, Gong Z, Wan W, Li J, et al. Requirement for p62 acetylation in the aggregation of ubiquitylated proteins under nutrient stress. Nat Commun. 2019;10(1): 5792.

CAS  Google Scholar 

Yang M, Qin Z, Lin Y, Ma D, Sun C, Xuan H, et al. HDAC10 switches NLRP3 modification from acetylation to ubiquitination and attenuates acute inflammatory diseases. Cell Commun Signal. 2024;22(1):615.

CAS  Google Scholar 

Shimizu K, Gi M, Suzuki S, North BJ, Watahiki A, Fukumoto S, et al. Interplay between protein acetylation and ubiquitination controls MCL1 protein stability. Cell Rep. 2021;37(6): 109988.

CAS  Google Scholar 

Xie Q, Hu B, Li H. Acetylation- and ubiquitination-regulated SFMBT2 acts as a tumor suppressor in clear cell renal cell carcinoma. Biol Direct. 2024;19(1):37.

CAS  Google Scholar 

Wang M, Mu G, Qiu B, Wang S, Tao C, Mao Y, et al. Competitive antagonism of KAT7 crotonylation against acetylation affects procentriole formation and colorectal tumorigenesis. Nat Commun. 2025;16(1):2379.

CAS  Google Scholar 

Martinez-Hernandez J, Parato J, Sharma A, Soleilhac JM, Qu X, Tein E, et al. Crosstalk between acetylation and the tyrosination/detyrosination cycle of alpha-tubulin in Alzheimer’s disease. Front Cell Dev Biol. 2022;10: 926914.

Google Scholar 

Zhang YY, Ning BT. Signaling pathways and intervention therapies in sepsis. Signal Transduct Tar. 2021;6(1):407.

Google Scholar 

Tang D, Kang R, Zeh HJ, Lotze MT. The multifunctional protein HMGB1: 50 years of discovery. Nat Rev Immunol. 2023;23(12):824–41.

CAS  Google Scholar 

Deng M, Scott MJ, Fan J, Billiar TR. Location is the key to function: HMGB1 in sepsis and trauma-induced inflammation. J Leukoc Biol. 2019;106(1):161–9.

CAS  Google Scholar 

Chen R, Kang R, Tang D. The mechanism of HMGB1 secretion and release. Exp Mol Med. 2022;54(2):91–102.

CAS 

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