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Welcome everyone to Chapter 4 of
this short talk series on
nuclear receptors as
therapeutic targets.
In Chapter 4 and the
consecutive Chapter 5,
we will have a look
at the structural and
the molecular mechanisms of
nuclear receptor activity,
and we will start in Chapter
4 with the mechanisms of
DNA interaction and the
role of dimerization.
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In Chapter 2, we have seen
the classification
of nuclear receptors
based on their
cellular localization
and their dimerization.
Remember that the steroid
hormone receptors of
the NR3 family here
on the left are
Type I nuclear receptors
and are localized in
the cytosol, bound to
heat shock proteins in
the absence of a ligand.
Upon agonist binding,
the receptor dissociates
from the heat shock protein,
forms a homodimer,
and translocates to the
nucleus to bind to the DNA.
The other nuclear receptors
belonging to the Type II,
III, and IV, in contrast,
are typically localized
in the nucleus
and bound to DNA also in
the absence of ligands.
They act in different
mono or oligomeric forms,
depending on what type they
are, and they often form
heterodimers with RXR or
homodimers or monomers.
It should be noted that
several nuclear receptors
of this Type II, III, and IV
can act in more than one of
these forms, so the association
to Type II, III, and IV
is not always exact.
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Here you see an overview of
the nuclear receptor family
with the receptors
labeled according to
their DNA interaction
classification
as Type I, II, III, or IV.
Only steroid hormone
receptors in
the middle and labeled in
violet belong to Class I,
which translocate to the
nucleus after ligand binding,
and then act as homodimers.
The majority of
nuclear receptors
in the NR1 family on the left,
mainly act as heterodimers
with a retinoid X receptor,
abbreviated as RXR,
and they are labeled in blue,
and some of them can
additionally act as a monomer.
revERB receptors and retinoic
acid receptor-related
orphan receptors
also belonging to
the NR1 family on the
left and labeled in red,
typically act as
monomers or homodimers.
The NR2 and NR4 families,
labeled orange,
can be active in all
three forms, whereas,
NR5 receptors, labeled in
green, act only as monomers,
and NR6, in brown,
only form homodimers,
according to current
understanding.
The three RXRs, labeled in
light blue in the middle,
are the universal
heterodimer partner for
other nuclear receptors,
and the NR0 receptors,
DAX1 and SHP, on
the upper right lack a DNA
binding domain as we have seen,
so they are not included in
the classification according
to DNA interaction type.
