HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention

@article{Yang2007HATsAH,
  title={HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention},
  author={X.–J. Yang and Edward Seto},
  journal={Oncogene},
  year={2007},
  volume={26},
  pages={5310-5318}
}
Acetylation of the ɛ-amino group of a lysine residue was first discovered with histones in 1968, but the responsible enzymes, histone acetyltransferases and deacetylases, were not identified until the mid-1990s. In the past decade, knowledge about this modification has exploded, with targets rapidly expanding from histones to transcription factors and other nuclear proteins, and then to cytoskeleton, metabolic enzymes, and signaling regulators in the cytoplasm. Thus, protein lysine acetylation… 

Targeting protein acetylation for improving cancer therapy.

The recent observation showing acetylation of proteins by calreticulin with a high efficiency when polyphenolic acetates are the acetyl group donating molecules and acetyl CoA as weak substrate extends the realm of protein acetylations beyond HAT/HDAC combination.

Roles of histone deacetylases in epigenetic regulation: emerging paradigms from studies with inhibitors

The zinc-dependent mammalian histone deacetylase (HDAC) family comprises 11 enzymes, which have specific and critical functions in development and tissue homeostasis. Mounting evidence points to a

Roles of Histone Deacetylases and Inhibitors in Anticancer Therapy

The present review will focus on HDACs I, II and IV, the best known inhibitors and potential alternative inhibitors derived from natural and synthetic products which can be used to influence HDAC activity and the development of new cancer therapies.

Enzymatic Mechanisms and Chemical Probes of the Myst Family of Histone Acetyltransferases

Kinetic study demonstrated that the acetylation of the active site lysine on MYST HATs marginally modulates the HAT catalysis, providing new insights into the regulatory mechanism of MYST catalysis.

NAD+‐dependent histone deacetylases (sirtuins) as novel therapeutic targets

An overview over sirtuins including their biology, targets, inhibitors, and activators and their potential as new therapeutic agents is presented.

Histone deacetylases: salesmen and customers in the post‐translational modification market

This review summarizes aspects of the current knowledge on the biological role and enzymology of the phosphorylation, acetylation, ubiquitylation and sumoylation of HDACs.

Lysine Acetylation/Deacetylation Modification of Immune-Related Molecules in Cancer Immunotherapy

The present review may provide a reference for researchers in the relevant field of study with the aim of being instructive and meaningful to further research as well as the selection of potential targets and effective measures for future cancer immunotherapy strategies.
...

References

SHOWING 1-10 OF 153 REFERENCES

Chemistry of acetyl transfer by histone modifying enzymes: structure, mechanism and implications for effector design

What is learned from the structures and related biochemistry of HATs and HDACs and the implications of these findings for the design of protein effectors to regulate gene expression and treat disease are discussed.

Histone acetyltransferases.

This review discusses the current understanding of histone acetyl transferases (HATs) or acetyltransferases (ATs): their discovery, substrate specificity, catalytic mechanism, regulation, and functional links to transcription, as well as to other chromatin-modifying activities.

Class IIa histone deacetylases: regulating the regulators

This review summarizes the latest discoveries in the field and discusses the molecular and structural determinants of class IIa HDACs regulation, emphasizing that comprehension of the mechanisms underlying class IIb HDAC functions is essential for potential therapeutic applications.

Orchestration of chromatin-based processes: mind the TRRAP

TRRAP appears to be responsible for a concerted and context-dependent recruitment of HATs and coordination of distinct chromatin-based processes, suggesting that its deregulation may contribute to diseases.

NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs

The recent findings about the functional relationship between H4K16 and the Sir2 class of deacetylases and how that relationship might impact aging and diseases including cancer and diabetes are reviewed.

Histone deacetylase inhibitors in cancer therapy

Although still early in drug development, there is a picture that is starting to develop as to the common toxicities and which tumors seem to be the most susceptible to this class of drugs.

Histone deacetylases, transcriptional control, and cancer

A key event in the regulation of eukaryotic gene expression is the posttranslational modification of nucleosomal histones, which converts regions of chromosomes into transcriptionally active or

Metabolism, cytoskeleton and cellular signalling in the grip of protein Nϵ ‐ and O‐acetylation

Nϵ‐ and O‐acetylation are becoming recognized as two prominent mechanisms for regulating protein functions in diverse organisms.
...