Effect of antisense menin on Smad heterodimerization, Smad nuclear
accumulation, and formation of Smad/DNA complexes. (a)
Effect of antisense menin (AS) on Smad2/3 and Smad4
heterodimerization. Myc-tagged Smad2 or Smad3 and flag-tagged Smad4
constructs were transfected (as indicated) into COS7 cells with or
without antisense menin. Transfected cells were treated (+) or not (−)
with 200 pM TGF-β for 1 h after overnight serum starvation. Cell
extracts were immunoprecipitated with anti-Smad2/3 antibody followed
by immunoblotting with anti-flag antibody. Expression of myc, flag, or
menin was monitored. W, Western blot; IP, immunoprecipitation.
(b) Effect of antisense menin (AS) on Smad2 and Smad3
nuclear accumulation. Nuclear extracts of Chinese hamster ovary cells
transfected or not with the antisense menin were cultured in the
absence or presence of 200 pM TGF-β and immunoblotted with Smad2/3,
Stat3, and menin antibodies. V, empty vector. (c) Effect
of antisense menin on the Smad3/4-DNA complex. GH4C1 cells were
transfected with myc-Smad3 and flag-Smad4 in the presence or absence of
antisense menin. Nuclear extracts were subjected to EMSA; a 29-bp
double-stranded oligonucleotide derived from the PAI-1 promoter
sequence of 3TP-Lux was used as probe. The shifted band is indicated by
the arrow; it was decreased in intensity by antisense menin and by
anti-myc antibodies (*). Menin and Smad3/4 in the nuclear
extracts were monitored.