Structural and functional characterization of the transforming growth factor-beta -induced Smad3/c-Jun transcriptional cooperativity

J Qing, Y Zhang, R Derynck
Journal of Biological Chemistry 2000 December 8, 275 (49): 38802-12
Smads are intracellular proteins that act as central effectors for transforming growth factor-beta (TGF-beta) and related proteins from the activated receptor into the nucleus, where they regulate ligand-induced gene expression. AP-1 binding sites have been functionally linked to the transcriptional activation of various genes in response to TGF-beta. Accordingly, we have previously shown that the heteromeric complex of Smad3 and Smad4 synergizes with c-Jun/c-Fos at the AP-1 binding site of the collagenase I promoter to induce transcriptional activation in response to TGF-beta. Using the collagenase I promoter as model system, we have now investigated the role of the c-Jun and Smad3 interactions with the promoter DNA and have further characterized the physical basis of the c-Jun/Smad3 interaction in the transcriptional response. Mutational analyses of the c-Jun protein and the AP-1 binding site in the promoter revealed that the interaction of c-Jun with DNA is necessary for transcriptional activation by TGF-beta and Smad3. Similar analyses of Smad3 and the Smad binding sites revealed that binding of Smad3 to DNA is also required, but that its DNA sequence-specific recognition is not essential. We also found that the basic leucine zipper domain of c-Jun and a short sequence close to the N terminus of Smad3 mediate their physical interaction, and that these regions are critical for their DNA-binding function. Our studies provide a basis for understanding the functional cooperativity of Smads with the diversity of transcription factors, which underlies the Smad-induced transcriptional activation in response to TGF-beta and related factors.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"