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Cancers and the NSD family of histone lysine methyltransferases.
[wolf-hirschhorn syndrome]
Both
genetic
and
epigenetic
alterations
are
responsible
for
the
stepwise
initiation
and
progression
of
cancers
.
Only
epigenetic
aberrations
can
be
reversible
,
allowing
the
malignant
cell
population
to
revert
to
a
more
benign
phenotype
.
The
epigenetic
therapy
of
cancers
is
emerging
as
an
effective
and
valuable
approach
to
both
the
chemotherapy
and
the
chemoprevention
of
cancer
.
The
utilization
of
epigenetic
targets
that
include
histone
methyltransferase
(
HMTase
)
,
Histone
deacetylatase
,
and
DNA
methyltransferase
,
are
emerging
as
key
therapeutic
targets
.
The
nuclear
receptor
binding
SET
domain
(
NSD
)
protein
is
a
family
of
three
HMTases
,
NSD
1
,
NSD
2
/
MMSET
/
WHSC
1
,
and
NSD
3
/
WHSC
1
L
1
,
and
plays
a
critical
part
in
chromatin
integrity
as
evidenced
by
a
growing
number
of
conditions
linked
to
the
alterations
and
/
or
amplification
of
NSD
1
,
NSD
2
,
and
/
or
NSD
3
.
NSD
1
,
NSD
2
and
NSD
3
are
associated
with
multiple
cancers
.
The
amplification
of
either
NSD
1
or
NSD
2
triggers
the
cellular
transformation
and
thus
is
key
in
the
early
carcinogenesis
events
.
In
most
cases
,
reducing
the
levels
of
NSD
proteins
would
suppress
cancer
growth
.
NSD
1
and
NSD
2
were
isolated
as
genes
linked
to
developmental
diseases
,
such
as
Sotos
syndrome
and
Wolf-
Hirschhorn
syndrome
,
respectively
,
implying
versatile
aspects
of
the
NSD
proteins
.
The
NSD
pathways
,
however
,
are
not
well
understood
.
It
is
noteworthy
that
the
NSD
family
is
phylogenetically
distinct
compared
to
other
known
lysine-
HMTases
,
Here
,
we
review
the
current
knowledge
on
NSD
1
/
NSD
2
/
NSD
3
in
tumorigenesis
and
prospect
their
special
value
for
developing
novel
anticancer
drugs
.
Diseases
Validation
Diseases presenting
"such as sotos syndrome and wolf-hirschhorn syndrome"
symptom
wolf-hirschhorn syndrome
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