Human Smad3 and Smad4 are sequence-specific transcription activators.
Mounting evidence indicates that Smad proteins are required for TGF beta signaling, but the way(s) in which Smad proteins propagate this signal is unclear. We found that two human Smad proteins (Smad3 and Smad4) could specifically recognize an identical 8 bp palindromic sequences (GTCTAGAC). Tandem repeats of this palindrome conferred striking TGF beta responsiveness to a minimal promoter. This responsiveness was abrogated by targeted deletion of the cellular Smad4 gene. These results define a novel biochemical property of Smad proteins that is likely to play a direct role in the biologic responses to TGF beta and related ligands.
Zawel
L
L
Molecular Genetics Laboratory, Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
Dai
J L
JL
Buckhaults
P
P
Zhou
S
S
Kinzler
K W
KW
Vogelstein
B
B
Kern
S E
SE
D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000235:genetics; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta