10938097

pubmed:Citation

17

The winged-helix (WH) BF-1 gene, which encodes brain factor 1 (BF-1) (also known as foxg1), is essential for the proliferation of the progenitor cells of the cerebral cortex. Here we show that BF-1-deficient telencephalic progenitor cells are more apt to leave the cell cycle in response to transforming growth factor beta (TGF-beta) and activin. We found that ectopic expression of BF-1 in vitro inhibits TGF-beta mediated growth inhibition and transcriptional activation. Surprisingly, we found that the ability of BF-1 to function as a TGF-beta antagonist does not require its DNA binding activity. Therefore, we investigated whether BF-1 can inhibit Smad-dependent transcriptional responses by interacting with Smads or Smad binding partners. We found that BF-1 does not interact with Smads. Because the identities of the Smad partners mediating growth inhibition by TGF-beta are not clearly established, we examined a model reporter system which is known to be activated by activin and TGF-beta through Smads and the WH factor FAST-2. We demonstrate that BF-1 associates with FAST-2. This interaction is dependent on the same region of protein which mediates its ability to interfere with the antiproliferative activity of TGF-beta and with TGF-beta-dependent transcriptional activation. Furthermore, the interaction of FAST-2 with BF-1 is mediated by the same domain which is required for FAST-2 to interact with Smad2. We propose a model in which BF-1 interferes with transcriptional responses to TGF-beta by interacting with FAST-2 or with other DNA binding proteins which function as Smad2 partners and which have a common mode of interaction with Smad2.

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http://linkedlifedata.com/resource/pubmed/journal/8109087

http://linkedlifedata.com/resource/pubmed/chemical/Activins, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Foxd1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Foxh1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Inhibins, http://linkedlifedata.com/resource/pubmed/chemical/Luciferases, http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Smad2 Protein, http://linkedlifedata.com/resource/pubmed/chemical/Smad2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta, http://linkedlifedata.com/resource/pubmed/chemical/beta-Galactosidase

Sep

pubmed-author:DowEE, pubmed-author:LalFF, pubmed-author:LeeJJ, pubmed-author:LinKK, pubmed-author:LisHH, pubmed-author:MassagueJJ, pubmed-author:XuanSS

20

Y

2009-11-18