Keywords Anticancer drugs, Epigenetics, Histone deacetylases, Zinc
metalloenzymes
Abbreviations
BCL2
B-cell lymphoma 2
CoREST
Corepressor RE1 silencing transcription factor
EGFR
Epidermal growth factor receptor
EMA
European medicines agency
FDA
Food and drug administration
HAT
Histone acetyltransferase
HDAC
Histone deacetylase
HMG-CoA 3-Hydroxy-3-methyl-glutaryl-coenzyme A
MiDAC
Mitotic deacetylase complex
NcoR
Nuclear receptor corepressor
NODE
Nanog and Oct4-associated deacetylase
NuRD
Nucleosome remodeling deacetylase
PI3K
Phosphatidylinositol 3-kinase
SAHA
Suberoylanilide hydroxamic acid
Sin3
Septation initiation network transcriptional regulatory protein 3
SMRT
Silencing mediator of retinoid and thyroid receptors
1 The Reversible Acetylation of Lysine Residues in Proteins
Fifty-five years ago, Philipps demonstrated that a significant proportion of lysine
residues in histone proteins are acetylated [1]. Shortly thereafter, Allfrey provided
evidence that acetylation is rapidly introduced in minutes after protein translation
and suggested that it is a mechanism for activating gene transcription [2]. Evidence
was soon found for the existence of enzymes that perform histone acetylation and its
reversal through deacetylation [3, 4]. These early studies laid the foundation for our
present understanding of histone acetylation as a regulator of eukaryotic gene
transcription. In the forward direction, the family of histone acetyltransferases
(HATs) transfers the acetyl group from the biological acyl donor acetyl coenzyme
A to histone proteins (Fig. 1) [5]. In addition, the reactive thioester group in acetyl
coenzyme A can undergo direct nonenzymatic transfer to protein substrates [6]. Conversely, the histone deacetylases (HDACs) hydrolyse acetyllysine back to lysine,
and it is the balance between these two dynamic processes that determines the
transcriptional state of eukaryotic cells.
2
A. Ganesan
metalloenzymes
Abbreviations
BCL2
B-cell lymphoma 2
CoREST
Corepressor RE1 silencing transcription factor
EGFR
Epidermal growth factor receptor
EMA
European medicines agency
FDA
Food and drug administration
HAT
Histone acetyltransferase
HDAC
Histone deacetylase
HMG-CoA 3-Hydroxy-3-methyl-glutaryl-coenzyme A
MiDAC
Mitotic deacetylase complex
NcoR
Nuclear receptor corepressor
NODE
Nanog and Oct4-associated deacetylase
NuRD
Nucleosome remodeling deacetylase
PI3K
Phosphatidylinositol 3-kinase
SAHA
Suberoylanilide hydroxamic acid
Sin3
Septation initiation network transcriptional regulatory protein 3
SMRT
Silencing mediator of retinoid and thyroid receptors
1 The Reversible Acetylation of Lysine Residues in Proteins
Fifty-five years ago, Philipps demonstrated that a significant proportion of lysine
residues in histone proteins are acetylated [1]. Shortly thereafter, Allfrey provided
evidence that acetylation is rapidly introduced in minutes after protein translation
and suggested that it is a mechanism for activating gene transcription [2]. Evidence
was soon found for the existence of enzymes that perform histone acetylation and its
reversal through deacetylation [3, 4]. These early studies laid the foundation for our
present understanding of histone acetylation as a regulator of eukaryotic gene
transcription. In the forward direction, the family of histone acetyltransferases
(HATs) transfers the acetyl group from the biological acyl donor acetyl coenzyme
A to histone proteins (Fig. 1) [5]. In addition, the reactive thioester group in acetyl
coenzyme A can undergo direct nonenzymatic transfer to protein substrates [6]. Conversely, the histone deacetylases (HDACs) hydrolyse acetyllysine back to lysine,
and it is the balance between these two dynamic processes that determines the
transcriptional state of eukaryotic cells.
2
A. Ganesan