The Role of Protein Acetylation in Carcinogenesis and Targeted Drug Discovery

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2022 Sep 29

PMID 36171897

Authors

Jingru Yang

Cong Song

Xianquan Zhan

Affiliations

Soon will be listed here.

Abstract

Protein acetylation is a reversible post-translational modification, and is involved in many biological processes in cells, such as transcriptional regulation, DNA damage repair, and energy metabolism, which is an important molecular event and is associated with a wide range of diseases such as cancers. Protein acetylation is dynamically regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) in homeostasis. The abnormal acetylation level might lead to the occurrence and deterioration of a cancer, and is closely related to various pathophysiological characteristics of a cancer, such as malignant phenotypes, and promotes cancer cells to adapt to tumor microenvironment. Therapeutic modalities targeting protein acetylation are a potential therapeutic strategy. This article discussed the roles of protein acetylation in tumor pathology and therapeutic drugs targeting protein acetylation, which offers the contributions of protein acetylation in clarification of carcinogenesis, and discovery of therapeutic drugs for cancers, and lays the foundation for precision medicine in oncology.

Citing Articles

Post-Translational Modifications of Proteins Orchestrate All Hallmarks of Cancer.

Bruno P, Arshad A, Gogu M, Waterman N, Flack R, Dunn K Life (Basel). 2025; 15(1).

PMID: 39860065 PMC: 11766951. DOI: 10.3390/life15010126.

O-GlcNAcylation in ovarian tumorigenesis and its therapeutic implications.

Xia L, Mei J, Huang M, Bao D, Wang Z, Chen Y Transl Oncol. 2024; 51:102220.

PMID: 39616984 PMC: 11647086. DOI: 10.1016/j.tranon.2024.102220.

Targeting PGK1: A New Frontier in Breast Cancer Therapy Under Hypoxic Conditions.

Cui J, Chai S, Liu R, Shen G Curr Issues Mol Biol. 2024; 46(11):12214-12229.

PMID: 39590319 PMC: 11593045. DOI: 10.3390/cimb46110725.

Acetylation of Histone H3 in Cancer Progression and Prognosis.

Miziak P, Baran M, Borkiewicz L, Trombik T, Stepulak A Int J Mol Sci. 2024; 25(20).

PMID: 39456765 PMC: 11507103. DOI: 10.3390/ijms252010982.

Role of Sam68 in different types of cancer (Review).

Jimenez-Cortegana C, Sanchez-Jimenez F, de la Cruz-Merino L, Sanchez-Margalet V Int J Mol Med. 2024; 55(1).

PMID: 39450529 PMC: 11537268. DOI: 10.3892/ijmm.2024.5444.

References

Knipstein J, Gore L . Entinostat for treatment of solid tumors and hematologic malignancies. Expert Opin Investig Drugs. 2011; 20(10):1455-67. DOI: 10.1517/13543784.2011.613822. View

Diallo I, Seve M, Cunin V, Minassian F, Poisson J, Michelland S . Current trends in protein acetylation analysis. Expert Rev Proteomics. 2018; 16(2):139-159. DOI: 10.1080/14789450.2019.1559061. View

Wu J, Zhang L, Feng Y, Khadka B, Fang Z, Liu J . HDAC8 promotes daunorubicin resistance of human acute myeloid leukemia cells via regulation of IL-6 and IL-8. Biol Chem. 2021; 402(4):461-468. DOI: 10.1515/hsz-2020-0196. View

Li Z, Hou Y, Hao G, Pan X, Fei H, Wang F . CUDC-907 enhances TRAIL-induced apoptosis through upregulation of DR5 in breast cancer cells. J Cell Commun Signal. 2020; 14(4):377-387. PMC: 7642015. DOI: 10.1007/s12079-020-00558-3. View

Dastjerdi M, Salahshoor M, Mardani M, Hashemibeni B, Roshankhah S . The effect of CTB on P53 protein acetylation and consequence apoptosis on MCF-7 and MRC-5 cell lines. Adv Biomed Res. 2013; 2:24. PMC: 3748634. DOI: 10.4103/2277-9175.108005. View

Choi H, An G, Baek M, Yoo E, Chai J, Lee Y . BET inhibitor suppresses migration of human hepatocellular carcinoma by inhibiting SMARCA4. Sci Rep. 2021; 11(1):11799. PMC: 8175750. DOI: 10.1038/s41598-021-91284-2. View

He B, Dai L, Zhang X, Chen D, Wu J, Feng X . The HDAC Inhibitor Quisinostat (JNJ-26481585) Supresses Hepatocellular Carcinoma alone and Synergistically in Combination with Sorafenib by G0/G1 phase arrest and Apoptosis induction. Int J Biol Sci. 2018; 14(13):1845-1858. PMC: 6231215. DOI: 10.7150/ijbs.27661. View

Choudhary C, Weinert B, Nishida Y, Verdin E, Mann M . The growing landscape of lysine acetylation links metabolism and cell signalling. Nat Rev Mol Cell Biol. 2014; 15(8):536-50. DOI: 10.1038/nrm3841. View

Gridelli C, Rossi A, Maione P . The potential role of histone deacetylase inhibitors in the treatment of non-small-cell lung cancer. Crit Rev Oncol Hematol. 2008; 68(1):29-36. DOI: 10.1016/j.critrevonc.2008.03.002. View

10.

Yang H, Wei L, Xun Y, Yang A, You H . BRD4: An emerging prospective therapeutic target in glioma. Mol Ther Oncolytics. 2021; 21:1-14. PMC: 8010576. DOI: 10.1016/j.omto.2021.03.005. View

11.

Islam A, Yang Y, Wu W, Chueh P, Lin M . Capsaicin attenuates cell migration via SIRT1 targeting and inhibition to enhance cortactin and β-catenin acetylation in bladder cancer cells. Am J Cancer Res. 2019; 9(6):1172-1182. PMC: 6610058. View

12.

Ribrag V, Kim W, Bouabdallah R, Lim S, Coiffier B, Illes A . Safety and efficacy of abexinostat, a pan-histone deacetylase inhibitor, in non-Hodgkin lymphoma and chronic lymphocytic leukemia: results of a phase II study. Haematologica. 2017; 102(5):903-909. PMC: 5477609. DOI: 10.3324/haematol.2016.154377. View

13.

Tiffon C, Adams J, van der Fits L, Wen S, Townsend P, Ganesan A . The histone deacetylase inhibitors vorinostat and romidepsin downmodulate IL-10 expression in cutaneous T-cell lymphoma cells. Br J Pharmacol. 2011; 162(7):1590-602. PMC: 3057296. DOI: 10.1111/j.1476-5381.2010.01188.x. View

14.

Ganai S . Histone deacetylase inhibitor givinostat: the small-molecule with promising activity against therapeutically challenging haematological malignancies. J Chemother. 2016; 28(4):247-54. DOI: 10.1080/1120009X.2016.1145375. View

15.

Wang C, Fu M, Mani S, Wadler S, Senderowicz A, Pestell R . Histone acetylation and the cell-cycle in cancer. Front Biosci. 2001; 6:D610-29. DOI: 10.2741/1wang1. View

16.

Spriano F, Gaudio E, Cascione L, Tarantelli C, Melle F, Motta G . Antitumor activity of the dual BET and CBP/EP300 inhibitor NEO2734. Blood Adv. 2020; 4(17):4124-4135. PMC: 7479962. DOI: 10.1182/bloodadvances.2020001879. View

17.

Falkenberg K, Johnstone R . Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat Rev Drug Discov. 2014; 13(9):673-91. DOI: 10.1038/nrd4360. View

18.

Feng L, Wang G, Chen Y, He G, Liu B, Liu J . Dual-target inhibitors of bromodomain and extra-terminal proteins in cancer: A review from medicinal chemistry perspectives. Med Res Rev. 2021; 42(2):710-743. PMC: 8837683. DOI: 10.1002/med.21859. View

19.

Bagratuni T, Mavrianou N, Gavalas N, Tzannis K, Arapinis C, Liontos M . JQ1 inhibits tumour growth in combination with cisplatin and suppresses JAK/STAT signalling pathway in ovarian cancer. Eur J Cancer. 2020; 126:125-135. DOI: 10.1016/j.ejca.2019.11.017. View

20.

Lan R, Wang Q . Deciphering structure, function and mechanism of lysine acetyltransferase HBO1 in protein acetylation, transcription regulation, DNA replication and its oncogenic properties in cancer. Cell Mol Life Sci. 2019; 77(4):637-649. PMC: 11104888. DOI: 10.1007/s00018-019-03296-x. View