GABPα and -β stimulate, in concert with p300,
the activity of IL-16 promoter. (A) GABPα and -β
stimulate the IL-16 promoter. Jurkat cells were cotransfected with a
luciferase reporter gene controlled by the IL-16 promoter (from −408
to +88), SRSPA-based vectors expressing GABPα or -β, or both, as
indicated. The cells were left untreated or stimulated with TPA (10
ng/ml) for 24 h. (B) The GABP-binding sites within
the IL-16 promoter are of crucial importance for its activity. Human
293 cells were transfected with a wild-type IL-16 promoter/luciferase
gene construct or mutated IL-16 promoter/luciferase constructs alone
or together with vectors expressing GABPα and -β. CmDm, mutations
in the ERE-C and ERE-D motifs (see Fig. 4B); INIm,
mutations within the +12 GABP site which overlaps the transcriptional
initiation site. (C) CBP/p300 enhance the activity of the
IL-16 promoter in a dose-dependent manner. 293 cells were cotransfected
with a luciferase reporter gene controlled by the IL-16 promoter (from
−408 to +88) and 0–50 ng of a p300 expression vector as indicated.
(D) Interaction between GABPα and p300. Equal amounts of
bacterially expressed glutathione S-transferase/p300
fusion proteins spanning N-terminal, middle, or C-terminal portions of
p300 immobilized on glutathione agrose beads were incubated with 500 ng
of bacterially expressed GABPα, -β or -α+β. The bound proteins
were eluted and immunodetected by using a mix of GABPα+β-specific
Abs. As a control for p300/GABP interaction, a glutathione
S-transferase fusion protein containing the N-terminal
transacting domain of NF-ATc (TADNF-ATc, 113–205) was used. In lane
13, 50 μg of nuclear proteins from 293 cells were fractionated. The
appearance of a weak GABPα band in lane 11 is the result of an
accidental contamination of the GABPβ protein preparation with
GABPα. The appearance of a second GABPα band in many lanes is
probably a GABPα cleavage product. The lowest strong band is most
likely the result of the crossreactivity of GABP Abs with a bacterial
protein binding unspecifically to p300.