Aberrant lysine acetylation in tumorigenesis: Implications in the development of therapeutics

Kaypee, Stephanie; Sudarshan, Deepthi; Shanmugam, Muthu K.; Mukherjee, Debanjan; Sethi, Gautam; Kundu, Tapas K.

doi:10.1016/j.pharmthera.2016.01.011

Cited by 71 publications

(56 citation statements)

References 348 publications

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“…Dysfunctions in the balance between KATs and KDACs are therefore associated with a variety of diseases such as cancer (see section 5.2), diabetes, cardiac hypertrophy, neurodegenerative disorders (see section 5.4), autoimmunity, asthma and retroviral pathogenesis [16,320,[351][352][353][354].…”

Section: Aberrant Lysine Acetylation and Its Implications In Diseasementioning

confidence: 99%

The world of protein acetylation

Drazic

Myklebust

Ree

et al. 2016

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

646

532

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Acetylation is one of the major post-translational protein modifications in the cell, with manifold effects on the protein level as well as on the metabolome level. The acetyl group, donated by the metabolite acetyl-coenzyme A, can be co- or post-translationally attached to either the α-amino group of the N-terminus of proteins or to the ε-amino group of lysine residues. These reactions are catalyzed by various N-terminal and lysine acetyltransferases. In case of lysine acetylation, the reaction is enzymatically reversible via tightly regulated and metabolism-dependent mechanisms. The interplay between acetylation and deacetylation is crucial for many important cellular processes. In recent years, our understanding of protein acetylation has increased significantly by global proteomics analyses and in depth functional studies. This review gives a general overview of protein acetylation and the respective acetyltransferases, and focuses on the regulation of metabolic processes and physiological consequences that come along with protein acetylation.

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Section: Aberrant Lysine Acetylation and Its Implications In Diseasementioning

confidence: 99%

The world of protein acetylation

Drazic

Myklebust

Ree

et al. 2016

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

646

532

View full text Add to dashboard Cite

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“…Histone acetylation modification is one of the important epigenetic regulatory methods, which functions as a regulator in numerous biological processes, including transcription, cell proliferation, differentiation, apoptosis and signal transduction 1,2 . The abnormality of histone lysine acetylation level is closely related to the occurrence of various diseases, especially in inflammation and tumour 3 . Bromodomain-containing proteins, readers of histone acetylation, function to regulate transcription programmes associated with phenotypic changes 4 .…”

Section: Introductionmentioning

confidence: 99%

Discovery of novel ATAD2 bromodomain inhibitors that trigger apoptosis and autophagy in breast cells by structure-based virtual screening

Zhang

Wang²,

Pan

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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ATAD2 has been reported to play an important role in the processes of numerous cancers and validated to be a potential therapeutic target. This work is to discover potent ATAD2 inhibitors and elucidate the underlying mechanisms in breast cancer. A novel ATAD2 bromodomain inhibitor (AM879) was discovered by combining structure-based virtual screening with biochemical analyses. AM879 presents potent inhibitory activity towards ATAD2 bromodomain (IC 50 ¼ 3565 nM), presenting no inhibitory activity against BRD2-4. Moreover, AM879 inhibited MDA-MB-231 cells proliferation with IC 50 value of 2.43 mM, suppressed the expression of c-Myc, and induced significant apoptosis. Additionally, AM978 could induce autophagy via PI3K-AKT-mTOR signalling in MDA-MB-231 cells. This study demonstrates the development of potent ATAD2 inhibitors with novel scaffolds for breast cancer therapy.

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“…Accumulating evidence has shown that protein acetylation is tightly associated with many human diseases such as cancers, cardiovascular diseases, diabetes and neurodegenerative disorders . Studies on protein acetylation have not only deepened our knowledge of its functions and mechanisms but also guided therapeutic strategies for acetylation‐associated diseases .…”

mentioning

confidence: 99%

Genetically encoding thioacetyl‐lysine as a non‐deacetylatable analog of lysine acetylation in Escherichia coli

et al. 2017

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Reversible lysine acetylation is one of the most widely distributed post‐translational modifications; it is involved in a variety of biological processes and can be found in all three domains of life. Acetyltransferases and deacetylases work coordinately to control levels of protein acetylation. In this work, we applied the genetic code expansion strategy to site‐specifically incorporate Nε‐thioacetyl‐l‐lysine (TAcK) as an analog of Nε‐acetyl‐l‐lysine (AcK) into green fluorescent protein and malate dehydrogenase in Escherichia coli. We showed that TAcK could serve as an ideal functional mimic for AcK. It could also resist the bacterial sirtuin‐type deacetylase CobB. Thus, genetic incorporation of TAcK as a non‐deacetylatable analog of AcK into proteins will facilitate in vivo studies of protein acetylation.

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Aberrant lysine acetylation in tumorigenesis: Implications in the development of therapeutics

Cited by 71 publications

References 348 publications

The world of protein acetylation

The world of protein acetylation

Discovery of novel ATAD2 bromodomain inhibitors that trigger apoptosis and autophagy in breast cells by structure-based virtual screening

Genetically encoding thioacetyl‐lysine as a non‐deacetylatable analog of lysine acetylation in Escherichia coli

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