Mutated or deleted p300/CBP genes have been reported in several solid cancers,
such as lung, colon, breast and ovarian carcinomas, nasopharyngeal carcinoma and
cutaneous squamous cell carcinoma (CSCC), and in most cases these mutations
result into the truncation of the proteins [40–45]. Loss of heterozygosity (LOH) at
the p300 locus has been observed in numerous cancers, including hepatocellular,
colorectal, oral, breast, ovarian, gastric carcinomas and glioblastomas [37]. Notably,
p300 is also involved in the regulation of expression and function of several
oncoproteins including c-myc [46], androgen receptor [47], tumour suppressor
protein BRCA1 [48] and p53 [49].
Like p300/CBP, MYST family members are often mutated in cancer, and chromosomal aberrations involving MOZ and MORF genes can drive leukaemogenesis.
In AML, both MOZ and MORF fuse with multiple genes, including CBP and p300
[28, 29]. These hybrid proteins lead to an aberrant acetylation and transcriptional
activation generally associated with overexpression of oncogenes. Recently, in vitro
and in vivo studies have demonstrated that the depletion of MORF expression
enhances cancer growth and aggressiveness of small-cell lung tumours [50].
Different and independent studies have also shown abnormal MOF expression,
and its corresponding acetylation mark (H4K16) has been found in certain primary
cancer tissues, including breast cancer, medulloblastoma, ovarian cancer, renal cell
carcinoma, colorectal carcinoma, gastric cancer as well as non-small-cell lung cancer
(NSCLC) [19]. However, the role of MOF in human tumorigenesis is still controversial and deserves more investigation. For example, MOF is frequently
downregulated and is a prognostic marker in colorectal, gastric, breast, ovarian,
hepatocellular and renal cell carcinomas [51–53]. Conversely, the overexpression of
MOF in NSCLC predicts poor prognosis of the disease [54].
The human Tip60 locus is frequently mutated or lost in a variety of tumours
including breast and prostate carcinomas [55]. Indeed, in prostate cancer Tip60 is
upregulated in clinical specimens, and its expression correlates with disease progression. Mechanistically, Tip60 acetylates the androgen receptor even in a ligandindependent manner, thus inducing the expression of target genes [55]. In breast
cancer, Bassi and coauthors have reported an interesting correlation between Tip60
levels and p53 mutations, thus suggesting that Tip60 is a novel breast tumour
suppressor gene [56].
Because of their cellular functions, also GNAT family members have been
implicated in different types of cancer. GCN5 is found to be upregulated in human
glioma, colon and lung cancer [57]. Conversely, PCAF gene is frequently deleted in
solid tumours such as ovarian cancer, gastric cancer and oesophageal carcinoma
[58]. Recent reports suggest that also α-TAT1 plays a key role in many cellular
processes related to cancer dissemination, including cell adhesion, migration and
invasion [17, 59, 60]. Notably, α-TAT1 is also associated with pancreatic cancerinitiating cells and breast cancer progression [61].
Histone Acetyltransferase Enzymes: From Biological Implications to Most. . .
101
such as lung, colon, breast and ovarian carcinomas, nasopharyngeal carcinoma and
cutaneous squamous cell carcinoma (CSCC), and in most cases these mutations
result into the truncation of the proteins [40–45]. Loss of heterozygosity (LOH) at
the p300 locus has been observed in numerous cancers, including hepatocellular,
colorectal, oral, breast, ovarian, gastric carcinomas and glioblastomas [37]. Notably,
p300 is also involved in the regulation of expression and function of several
oncoproteins including c-myc [46], androgen receptor [47], tumour suppressor
protein BRCA1 [48] and p53 [49].
Like p300/CBP, MYST family members are often mutated in cancer, and chromosomal aberrations involving MOZ and MORF genes can drive leukaemogenesis.
In AML, both MOZ and MORF fuse with multiple genes, including CBP and p300
[28, 29]. These hybrid proteins lead to an aberrant acetylation and transcriptional
activation generally associated with overexpression of oncogenes. Recently, in vitro
and in vivo studies have demonstrated that the depletion of MORF expression
enhances cancer growth and aggressiveness of small-cell lung tumours [50].
Different and independent studies have also shown abnormal MOF expression,
and its corresponding acetylation mark (H4K16) has been found in certain primary
cancer tissues, including breast cancer, medulloblastoma, ovarian cancer, renal cell
carcinoma, colorectal carcinoma, gastric cancer as well as non-small-cell lung cancer
(NSCLC) [19]. However, the role of MOF in human tumorigenesis is still controversial and deserves more investigation. For example, MOF is frequently
downregulated and is a prognostic marker in colorectal, gastric, breast, ovarian,
hepatocellular and renal cell carcinomas [51–53]. Conversely, the overexpression of
MOF in NSCLC predicts poor prognosis of the disease [54].
The human Tip60 locus is frequently mutated or lost in a variety of tumours
including breast and prostate carcinomas [55]. Indeed, in prostate cancer Tip60 is
upregulated in clinical specimens, and its expression correlates with disease progression. Mechanistically, Tip60 acetylates the androgen receptor even in a ligandindependent manner, thus inducing the expression of target genes [55]. In breast
cancer, Bassi and coauthors have reported an interesting correlation between Tip60
levels and p53 mutations, thus suggesting that Tip60 is a novel breast tumour
suppressor gene [56].
Because of their cellular functions, also GNAT family members have been
implicated in different types of cancer. GCN5 is found to be upregulated in human
glioma, colon and lung cancer [57]. Conversely, PCAF gene is frequently deleted in
solid tumours such as ovarian cancer, gastric cancer and oesophageal carcinoma
[58]. Recent reports suggest that also α-TAT1 plays a key role in many cellular
processes related to cancer dissemination, including cell adhesion, migration and
invasion [17, 59, 60]. Notably, α-TAT1 is also associated with pancreatic cancerinitiating cells and breast cancer progression [61].
Histone Acetyltransferase Enzymes: From Biological Implications to Most. . .
101