The role of protein acetylation in carcinogenesis and targeted drug discovery

Yang, Jingru; Song, Cong; Zhan, Xianquan

doi:10.3389/fendo.2022.972312

Cited by 18 publications

(15 citation statements)

References 300 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tubulin is the target of many anticancer drugs. 421 Tumors are resistant to apoptosis. PDCD5, a protein related to apoptosis, can bind to Tip60 and increase p53 acetylation at K120, which affects the expression of apoptosis‐related genes such as Bax .…”

Section: Acetylationmentioning

confidence: 99%

“…Increasing evidence shows that carcinogenesis is affected by metabolism in the body. Most metabolic proteins are substrates of lysine acetylation, 421 such as ATM, ABL1, CDK9, BTK, and CDK1. PKM2 is the last rate‐limiting enzyme in the glycolytic pathway responsible for the conversion of phosphoenolpyruvate to pyruvate.…”

Section: Acetylationmentioning

confidence: 99%

“…The acetylation of α‐tubulin, a component of the cytoskeleton, is an important indicator of microtubule stability. Tubulin is the target of many anticancer drugs 421 . Tumors are resistant to apoptosis.…”

Section: Acetylationmentioning

confidence: 99%

See 2 more Smart Citations

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

View full text Add to dashboard Cite

Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

show abstract

Section: Acetylationmentioning

confidence: 99%

Section: Acetylationmentioning

confidence: 99%

See 1 more Smart Citation

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

View full text Add to dashboard Cite

show abstract

“…Two families of antagonistic enzymes control histone acetylation: Histone acetyltransferases (HATs), which acetylate lysine residues at the N-terminus of histone proteins, and HDACs, which remove acetyl groups from histones. Histone acetylation reduces attraction between negative and positive charges of DNA and histone tails, respectively ( 90 , 91 ). This structural change favors the decompaction of chromatin, allowing access to the gene sequence for its transcription.…”

Section: Epigenetic Mechanisms In Cancer Roles In Carcinogenesis and ...mentioning

confidence: 99%

Modulating epigenetic modifications for cancer therapy (Review)

et al. 2023

View full text Add to dashboard Cite

Cancer is a global public health concern. Alterations in epigenetic processes are among the earliest genomic aberrations occurring during cancer development and are closely related to progression. Unlike genetic mutations, aberrations in epigenetic processes are reversible, which opens the possibility for novel pharmacological treatments. Non-coding RNAs (ncRNAs) represent an essential epigenetic mechanism, and emerging evidence links ncRNAs to carcinogenesis. Epigenetic drugs (epidrugs) are a group of promising target therapies for cancer treatment acting as coadjuvants to reverse drug resistance in cancer. The present review describes central epigenetic aberrations during malignant transformation and explains how epidrugs target DNA methylation, histone modifications and ncRNAs. Furthermore, clinical trials focused on evaluating the effect of these epidrugs alone or in combination with other anticancer therapies and other ncRNA-based therapies are discussed. The use of epidrugs promises to be an effective tool for reversing drug resistance in some patients with cancer. Contents1. Introduction 2. Epigenetic mechanisms in cancer, roles in carcinogenesis and therapeutic approaches 3. ncRNAs in epigenetic control 4. Conclusions

show abstract

“…Additionally, Seetharaman and colleagues have shown that the protein Talin recruits αTAT1 to the focal adhesions where the MT acetylation is critical for fine-tuning the mechanosensitive cell adhesion and migration [ 327 ]. This role of acetylated α-tubulin Lys40 in cell migration has been explored in oncology, with several studies targeting MT acetylation as a chemotherapeutic approach [ 328 ].…”

Section: Tubulin Acetylation: Structural and Functional Implicationsmentioning

confidence: 99%

Tubulin Post-Translational Modifications: The Elusive Roles of Acetylation

Carmona

Marinho

Matos

et al. 2023

Biology

View full text Add to dashboard Cite

Microtubules (MTs), dynamic polymers of α/β-tubulin heterodimers found in all eukaryotes, are involved in cytoplasm spatial organization, intracellular transport, cell polarity, migration and division, and in cilia biology. MTs functional diversity depends on the differential expression of distinct tubulin isotypes and is amplified by a vast number of different post-translational modifications (PTMs). The addition/removal of PTMs to α- or β-tubulins is catalyzed by specific enzymes and allows combinatory patterns largely enriching the distinct biochemical and biophysical properties of MTs, creating a code read by distinct proteins, including microtubule-associated proteins (MAPs), which allow cellular responses. This review is focused on tubulin-acetylation, whose cellular roles continue to generate debate. We travel through the experimental data pointing to α-tubulin Lys40 acetylation role as being a MT stabilizer and a typical PTM of long lived MTs, to the most recent data, suggesting that Lys40 acetylation enhances MT flexibility and alters the mechanical properties of MTs, preventing MTs from mechanical aging characterized by structural damage. Additionally, we discuss the regulation of tubulin acetyltransferases/desacetylases and their impacts on cell physiology. Finally, we analyze how changes in MT acetylation levels have been found to be a general response to stress and how they are associated with several human pathologies.

show abstract

The role of protein acetylation in carcinogenesis and targeted drug discovery

Cited by 18 publications

References 300 publications

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Modulating epigenetic modifications for cancer therapy (Review)

Tubulin Post-Translational Modifications: The Elusive Roles of Acetylation

Contact Info

Product

Resources

About