BF-1 interferes with transforming growth factor beta signaling by associating with Smad partners Journal Article
| Authors: | Dou, C.; Lee, J.; Liu, B.; Liu, F.; Massague, J.; Xuan, S. H.; Lai, E. |
| Article Title: | BF-1 interferes with transforming growth factor beta signaling by associating with Smad partners |
| Abstract: | 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, me 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 TGP-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. |
| Keywords: | oncoprotein; protein; expression; tgf-beta; cell-cycle arrest; dna-binding; transcriptional repressor; interacts; neocortical neuronogenesis; fork head |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 20 |
| Issue: | 17 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2000-09-01 |
| Start Page: | 6201 |
| End Page: | 6211 |
| Language: | English |
| ACCESSION: | WOS:000088716500003 |
| DOI: | 10.1128/mcb.20.17.6201-6211.2000 |
| PROVIDER: | wos |
| PMCID: | PMC86095 |
| PUBMED: | 10938097 |
| Notes: | Article -- Source: Wos |
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