| First Author | Theil T | Year | 1995 |
| Journal | J Biol Chem | Volume | 270 |
| Issue | 52 | Pages | 30958-64 |
| PubMed ID | 8537352 | Mgi Jnum | J:30561 |
| Mgi Id | MGI:78067 | Doi | 10.1074/jbc.270.52.30958 |
| Citation | Theil T, et al. (1995) Short isoform of POU factor Brn-3b can form a heterodimer with Brn-3a that is inactive for octamer motif binding. J Biol Chem 270(52):30958-64 |
| abstractText | The POU proteins Brn-3a and Brn-3b belong to a family of DNA binding transcription factors that share stretches of extensive homology. Both Brn-3a and Brn-3b are expressed as shorter and longer isoforms. The long form of Brn-3a is able to oncogenically transform primary fibroblasts. By contrast, the short form of Brn-3b (Brn-3b(s)) cannot transform fibroblasts but is able to specifically inhibit the transforming activity of Brn-3a(1). Moreover, Brn-3a(1) can act as a transcriptional transactivator, while Brn-3b(s) is not only unable to do so but in addition specifically inhibits the tranactivating activity of Brn-3a(1). Here, we show that the opposite and antagonistic activities of Brn-3a(1) and Brn-3b(s) proteins are due to their different DNA binding properties; Brn-3a(1) but not Brn-3b(s) can form stable complexes with several octamer-related target DNA sequences. The presence of Brn-3b(s) completely inhibits the binding of Brn-3a(1) to DNA by preventing the formation of Brn-3a(1)-DNA complexes as well as by disrupting preformed complexes. Experiments with GST fusion proteins and in vitro binding studies suggest that the inhibition of Brn-3a(1) activity by Brn-3b(s) occurs via direct interaction of the two transcription factors in solution. Therefore, we hypothesize that Brn-3b(s) can act as a direct antagonist of Brn-3a(1) by inhibiting its DNA binding through the formation of an inactive hetero-oligomeric complex. |
