Cancer drugs

1
Latent TGF-b complex
50-375 aa
110-140 aa
NH2
COOH
Leader
Pro-domain
Mature domain
SH
Proteolytic cleavage
LAP (latency associated peptide)
s
s
LTBP (latent TGF-b binding protein)
2
Developmental studies in fly/worm/Xenopus
Dpp, activin, Daf7
Noggin, Sog/chordin
Tkv, Sax, Punt, Daf1, 4
3
Cuticles phenotypes in dpp mutant embryos
WT
Weak phenotype
Strong phenotype
Raftery etal Genetics 139241
4
sog (short gastrulation) fly is defective in D/V
patterning
WT
sog null
rho(rhomboid) staining for amnioserosa
Francois etal GD 82602
5
Xenopus embryonic D/V patterning
organizer
6
Protease Inhibitor Signal Fly
Tolloid Sog Dpp Frog Xolloid Chordin BMP2/
4 Zebrafish Minifin Chordino Swirl
7
(No Transcript)
8
Growth control In tissue culture
Development in Fly/worms/Xenopus
Ligand TGF-b
Dpp, activin, Daf7, BMP
Noggin, Sog, chordin
LAP, LTBP,Inhibin follistatin
Receptors Type I, II, III TGF-b receptor
Tkv, Sax, Punt, Daf1, 4
Intracellular mediator Smads
Mad, Sma
Nuclear-gtcellular effects
Nuclear-gtorganismal effects
9
Isolation of Fly Mad (mother against dpp)
WT
dpphr4 Df(2L)C28/dppd6
dpphr4/dppd6
dpphr4 /dppd6Dp(23)JS20, Mad
Sekelsky etal Genetics 1391347