Top Med Chem (2020) 33: 429–454
DOI: 10.1007/7355_2019_81
© Springer Nature Switzerland AG 2019
Published online: 10 October 2019
Acetylation and Methylation in Asthma,
COPD, and Lung Cancer
Martijn R. H. Zwinderman, Fangyuan Cao, and Frank J. Dekker
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431
1.1 Epigenetics . . . . .. . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . 431
1.2 Epidrugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431
1.3 Protein Lysine Acetylation and Deacetylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 432
1.4 Relevance of Deacetylases in Disease and Their Potential as Drug Targets . . . . . . . . 432
2 Lysine Deacetylases in Asthma and COPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 433
2.1 Similarities and Differences Between Asthma and COPD . . . . . . . . . . . . . . . . . . . . . . . . . . . 433
2.2 Deacetylase and Acetyltransferase Expression in COPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . 434
2.3 Causes and Consequences of a Decrease in HDAC2 Expression in COPD . . . . . . . . . 434
2.4 Restoring HDAC2 Activity in COPD as a Therapeutic Strategy . . . . . . . . . . . . . . . . . . . . 436
2.5 Targeting HDAC Isoenzymes in COPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436
2.6 Deacetylase and Acetyltransferase Expression in Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . 438
2.7 Which HDAC to Inhibit in Asthma? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 439
3 Protein and DNA Methylation in Asthma and COPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 440
3.1 Cross Talk Between Acetylation and Methylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 441
3.2 DNA Methylation in Asthma and COPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442
3.3 Protein Methylation in Asthma and COPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 443
4 HDACi and DNMTi in Lung Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 444
5 Conclusions and Future Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 446
Abstract The urgent need for new therapies to treat airway diseases is exemplified
by the death of approximately three million patients suffering from chronic obstructive pulmonary disease (COPD) each year. Additionally, lung cancer is the most
M. R. H. Zwinderman, F. Cao, and F. J. Dekker (*)
Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy (GRIP),
University of Groningen, Groningen, The Netherlands
e-mail: r.h.zwinderman@rug.nl; f.cao@rug.nl; f.j.dekker@rug.nl