Keywords Cancer, Chemical probes, Epigenetics, Histone acetyltransferase
inhibitors, Structure- and ligand-based drug discovery
Abbreviations
ALL
Acute lymphoid leukaemia
AML
Acute myeloid leukaemia
BRD
Bromodomain
CBP
CREB-binding protein
CSCC
Cutaneous squamous cell carcinoma
DTT
Dithiothreitol
GCN5
General control nonderepressible 5
GNAT
Gcn5-related N-acetyltransferase
HATi
Histone acetyltransferase inhibitors
HATs
Histone acetyltransferases
HDACs
Histone deacetylases
LoCAMs
Long chain alkylidene malonates
LOH
Loss of heterozygosity
MSL
Male-specific lethal
MYST
Moz, Ybf2/Sas3, Sas2, Tip60
NCOA
Nuclear receptor coactivator
NSCLC
Non-small-cell lung cancer
NSL
Non-specific lethal
PCAF
p300/CBP-associated factor
SRC-1
Steroid receptor coactivator-1
SRC-3/AIB-1 Steroid receptor coactivator-3/activated in breast cancer-1
TAFII250
TATA box binding protein (TBP)-associated factor
TIF-2
Transcriptional intermediary factor-2
TRAM-1
Thyroid hormone receptor activator molecule-1
α-TAT1
α-Tubulin acetyltransferase 1
1 Background
Histone acetylation is one of most studied post-translational modifications involved
in a plethora of cell functions, including the regulation of gene expression [1]. The
balance between acetylation and deacetylation of histone proteins is regulated by the
action of two protein families: histone acetyltransferases (HATs) and histone
deacetylases (HDACs). HATs catalyse the transfer of an acetyl group from acetylCoA to the lysine (K) located near the amino terminus of core histone proteins
(Fig. 1). The reaction is preferentially carried out on specific lysine residues: for
94
D. Trisciuoglio and D. Rotili
inhibitors, Structure- and ligand-based drug discovery
Abbreviations
ALL
Acute lymphoid leukaemia
AML
Acute myeloid leukaemia
BRD
Bromodomain
CBP
CREB-binding protein
CSCC
Cutaneous squamous cell carcinoma
DTT
Dithiothreitol
GCN5
General control nonderepressible 5
GNAT
Gcn5-related N-acetyltransferase
HATi
Histone acetyltransferase inhibitors
HATs
Histone acetyltransferases
HDACs
Histone deacetylases
LoCAMs
Long chain alkylidene malonates
LOH
Loss of heterozygosity
MSL
Male-specific lethal
MYST
Moz, Ybf2/Sas3, Sas2, Tip60
NCOA
Nuclear receptor coactivator
NSCLC
Non-small-cell lung cancer
NSL
Non-specific lethal
PCAF
p300/CBP-associated factor
SRC-1
Steroid receptor coactivator-1
SRC-3/AIB-1 Steroid receptor coactivator-3/activated in breast cancer-1
TAFII250
TATA box binding protein (TBP)-associated factor
TIF-2
Transcriptional intermediary factor-2
TRAM-1
Thyroid hormone receptor activator molecule-1
α-TAT1
α-Tubulin acetyltransferase 1
1 Background
Histone acetylation is one of most studied post-translational modifications involved
in a plethora of cell functions, including the regulation of gene expression [1]. The
balance between acetylation and deacetylation of histone proteins is regulated by the
action of two protein families: histone acetyltransferases (HATs) and histone
deacetylases (HDACs). HATs catalyse the transfer of an acetyl group from acetylCoA to the lysine (K) located near the amino terminus of core histone proteins
(Fig. 1). The reaction is preferentially carried out on specific lysine residues: for
94
D. Trisciuoglio and D. Rotili