p300 at K685 enhances its DNA binding and transactivation activities, as well as its
nuclear localization [5]. Similarly, CBP acetylates c-myb and E2F1 thus increasing
their transactivating capacity [6]. Conversely, CBP-mediated acetylation of FoxO1
attenuates its DNA binding activity [10].
The GNAT family consists of 12 proteins with different cellular functions and
substrates, including GCN5 (general control nonderepressible 5; KAT2A), PCAF
(p300/CBP-associated factor, KAT2B), α-tubulin acetyltransferase 1 (α-TAT1),
HAT1, the elongator complex subunit Elp3, the mediator-complex subunit Nut1,
Hpa2 and other proteins showing a sequence and structural resemblance with GCN5.
GNAT proteins share a domain composed of four A–D conserved sequence motifs
and rarely have bromodomains or chromodomains required for binding acetylated or
methylated lysine, respectively. In general, GNAT family is involved in cell growth,
playing an important role in cell cycle regulation [11]. The two main members
GCN5 and PCAF are closely related proteins. GCN5 is needed for normal progression through the G2/M phases and mitotic gene expression. PCAF shares 73%
sequence homology with GCN5 and plays a role in transcriptional activation, cell
cycle arrest and cell differentiation. Under stress conditions, PCAF is required for
the acetylation of histone H3 on p21 promoter, thus stopping cell growth [12]. The
GNAT member α-TAT1 is the main responsible for α-tubulin acetylation at K40 in
higher organisms [13–15]. α-TAT1 is required for cell migration and invasion [16],
and its overexpression in breast cancer cells increases α-tubulin acetylation and
enhances formation of microtentacles, flexible cell protrusions enhancing the attachment of circulating cells [17].
The MYST family (acronym for the founding members MOZ, Ybf2, Sas2, TIP60)
is the largest but still poorly studied HAT family. Currently, it comprises five human
enzymes: Tip60, MOF, MOZ, MORF and HBO1. This family is characterized by the
presence of a highly conserved MYST domain containing acetyl-CoA binding and
zinc finger motifs [18]. Many MYSTs also contain other domains for recognition of
other proteins [19]. Moreover, they are involved in a wide range of cellular processes
including regulation of transcription, cell growth, cell cycle and stem cell differentiation [18]. Tip60 is the most studied MYST family member. This enzyme is mainly
involved in transcriptional regulation, acting as cofactor for different transcription
factor, including c-Myc [20], p53 [21] and E2F1 [22]. Beyond its role as transcriptional activator, Tip60 is implicated in multiple cellular pathways, including transcription, DNA damage-induced checkpoint activation and apoptosis [23, 24]. MOF
is a well-conserved member of the MYST family [25]. It plays important roles in
transcriptional activation by acetylating histone H4 on K16, a prevalent mark associated with chromatin de-condensation. The incorporation of MOF in distinct transcription regulatory complexes, namely, the MSL (male-specific lethal: MSL1,
MSL2) and the NSL (non-specific lethal: KANSL1, KANSL3, MCRS1) complexes,
is important for its enzymatic activity and target selection [26]. Recently, MOF and
MOF-associated complex have been found to be dual transcriptional regulators of
nuclear and mitochondrial genomes [27]. MOZ was firstly identified as a protein with
a zinc finger and a putative acetyltransferase signature that in the translocation t(8;16)
(p11;p13) of acute myeloid leukaemia (AML) is a fusion partner of the CBP.
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D. Trisciuoglio and D. Rotili
nuclear localization [5]. Similarly, CBP acetylates c-myb and E2F1 thus increasing
their transactivating capacity [6]. Conversely, CBP-mediated acetylation of FoxO1
attenuates its DNA binding activity [10].
The GNAT family consists of 12 proteins with different cellular functions and
substrates, including GCN5 (general control nonderepressible 5; KAT2A), PCAF
(p300/CBP-associated factor, KAT2B), α-tubulin acetyltransferase 1 (α-TAT1),
HAT1, the elongator complex subunit Elp3, the mediator-complex subunit Nut1,
Hpa2 and other proteins showing a sequence and structural resemblance with GCN5.
GNAT proteins share a domain composed of four A–D conserved sequence motifs
and rarely have bromodomains or chromodomains required for binding acetylated or
methylated lysine, respectively. In general, GNAT family is involved in cell growth,
playing an important role in cell cycle regulation [11]. The two main members
GCN5 and PCAF are closely related proteins. GCN5 is needed for normal progression through the G2/M phases and mitotic gene expression. PCAF shares 73%
sequence homology with GCN5 and plays a role in transcriptional activation, cell
cycle arrest and cell differentiation. Under stress conditions, PCAF is required for
the acetylation of histone H3 on p21 promoter, thus stopping cell growth [12]. The
GNAT member α-TAT1 is the main responsible for α-tubulin acetylation at K40 in
higher organisms [13–15]. α-TAT1 is required for cell migration and invasion [16],
and its overexpression in breast cancer cells increases α-tubulin acetylation and
enhances formation of microtentacles, flexible cell protrusions enhancing the attachment of circulating cells [17].
The MYST family (acronym for the founding members MOZ, Ybf2, Sas2, TIP60)
is the largest but still poorly studied HAT family. Currently, it comprises five human
enzymes: Tip60, MOF, MOZ, MORF and HBO1. This family is characterized by the
presence of a highly conserved MYST domain containing acetyl-CoA binding and
zinc finger motifs [18]. Many MYSTs also contain other domains for recognition of
other proteins [19]. Moreover, they are involved in a wide range of cellular processes
including regulation of transcription, cell growth, cell cycle and stem cell differentiation [18]. Tip60 is the most studied MYST family member. This enzyme is mainly
involved in transcriptional regulation, acting as cofactor for different transcription
factor, including c-Myc [20], p53 [21] and E2F1 [22]. Beyond its role as transcriptional activator, Tip60 is implicated in multiple cellular pathways, including transcription, DNA damage-induced checkpoint activation and apoptosis [23, 24]. MOF
is a well-conserved member of the MYST family [25]. It plays important roles in
transcriptional activation by acetylating histone H4 on K16, a prevalent mark associated with chromatin de-condensation. The incorporation of MOF in distinct transcription regulatory complexes, namely, the MSL (male-specific lethal: MSL1,
MSL2) and the NSL (non-specific lethal: KANSL1, KANSL3, MCRS1) complexes,
is important for its enzymatic activity and target selection [26]. Recently, MOF and
MOF-associated complex have been found to be dual transcriptional regulators of
nuclear and mitochondrial genomes [27]. MOZ was firstly identified as a protein with
a zinc finger and a putative acetyltransferase signature that in the translocation t(8;16)
(p11;p13) of acute myeloid leukaemia (AML) is a fusion partner of the CBP.
98
D. Trisciuoglio and D. Rotili