Biology Reference
In-Depth Information
Like BR-C,
E74
is directly induced by ecdysone and responsible for the
74EF early puff. Mutations in
E74
confer pupal lethality, indicating that this
gene plays essential roles during metamorphosis.
E74
produces two protein
isoforms, E74A and E74B, which share a C-terminal ETS DBD (
Burtis
et al., 1990
). Both isoforms are precisely controlled by changes in ecdysone
titers and display complementary profiles.
E74A
is induced when hormone
concentrations are high, while
E74B
is abundant when ecdysone concen-
trations have fallen to intermediate or lower levels. Correspondingly,
E74A
transcript levels fall when ecdysone concentrations start to decline,
and
E74B
mRNA is repressed by rising hormone titers. This behavioral link
between the two isoforms is critical for the proper timing of secondary gene
responses (
Fletcher, D'Avino, & Thummel, 1997; Karim & Thummel,
1991; Urness & Thummel, 1995
).
The
E75
early gene maps to the 75B early puff and encodes a member of
the nuclear receptor superfamily. E75 forms at least three protein isoforms
(E75A-C) (
Segraves & Hogness, 1990
). Like all
Drosophila
nuclear receptor
genes, alternative splicing tends to produce protein isoforms that differ in
their N-terminal sequences but share a common LBD in the C-terminus.
This is not any different for E75; however, the E75B isoform represents
an unusual nuclear receptor protein: While E75A and E75C both have a
complete DBD and LBD domain, splicing of
E75B
removes a part of the
DBD domain, which abolishes its ability to bind to DNA. This splice form
appears to be a fairly ancient invention, as its closest fly homolog,
E78
, also
generates a protein isoform (E78B) with a truncated DBD domain (
Stone &
Thummel, 1993
). Mutations specific for
E75B
are viable, however, molec-
ular data demonstrated that E75B binds to another nuclear receptor, DHR3,
in an inhibitory fashion to delay the induction of a third nuclear receptor,
b
FTZ-F1 (
White, Hurban, Watanabe, & Hogness, 1997
). It should be
noted that
E75B
null mutants do not display defects in the timing of
b
ftz-f1
expression, raising the possibility that E75B and E78B are function-
ally redundant (
Russell, Heimbeck, Goddard, Carpenter, & Ashburner,
1996; Stone & Thummel, 1993
).
In contrast to
E75B
, animals mutant for
E75A
display larval lethality,
molting defects, and developmental delays, while
E75C
is required for late
pupal development and adult viability (
Bialecki, Shilton, Fichtenberg,
Segraves, & Thummel, 2002
). In 2005, the Krause lab published the surpris-
ing finding that E75 binds with high affinity to heme (
Reinking et al., 2005
).
This led to the suggestion that the protein either acts as a heme or gas sensor.
A recent study from the same lab showed that E75 is a sensor for the signaling
