Suppression of MafA-dependent transcription by transforming growth factor-beta signaling.
MafA is a basic leucine zipper (b-Zip) type transcription factor that binds to the insulin promoter and regulates insulin transcription synergistically with Pdx-1 and NeuroD. Transforming growth factor-beta (TGF-beta) signaling has been reported to regulate activity of b-Zip transcription factor such as ATF-2 and acts as an important regulator of insulin gene transcription and pancreatic beta cell maintenance. To investigate the relationship between MafA-dependent transcriptional activation and TGF-beta signaling, we examined the effects of TGF-beta signal on MafA-dependent transactivation of the rat insulin II gene promoter (RIPII-251) and a synthetic MafA-dependent promoter. MafA-dependent activation of the reporters was inhibited in the presence of Smad2/Smad4 or Smad3/Smad4 and a constitutively active TGF-beta type I receptor and this inhibition was dependent upon the presence of MafA. Co-immunoprecipitation analyses revealed that MafA physically interacts with Smad2 or Smad3. These results suggest that MafA-dependent transcriptional activation is negatively regulated by TGF-beta signaling.
Matsumura
Haruka
H
Department of Anatomy and Embryology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Kudo
Takashi
T
Harada
Ayako
A
Esaki
Ritsuko
R
Suzuki
Hiroyuki
H
Kato
Mitsuyasu
M
Takahashi
Satoru
S
D000818:Animals; D006801:Humans; D007328:Insulin / Q000096:biosynthesis; D051473:Maf Transcription Factors, Large / Q000235:genetics / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic / Q000502:physiology; D051381:Rats; D015398:Signal Transduction; D051785:Smad Proteins / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000502:physiology*
D007328:Insulin; D051473:Maf Transcription Factors, Large; C485160:Mafa protein, mouse; D051785:Smad Proteins; D016212:Transforming Growth Factor beta