| First Author | Bein K | Year | 2011 |
| Journal | Am J Respir Cell Mol Biol | Volume | 45 |
| Issue | 2 | Pages | 436-44 |
| PubMed ID | 21148742 | Mgi Jnum | J:186817 |
| Mgi Id | MGI:5433276 | Doi | 10.1165/rcmb.2010-0260OC |
| Citation | Bein K, et al. (2011) JUN-CCAAT/enhancer-binding protein complexes inhibit surfactant-associated protein B promoter activity. Am J Respir Cell Mol Biol 45(2):436-44 |
| abstractText | The murine surfactant-associated protein B (Sftpb) gene promoter, spanning nucleotides -653 to +42, is composed of functionally distinct proximal and distal regions. Although both regions contain consensus/putative activator protein 1 (AP-1) sites, the distal, but not the proximal, region mediates the inhibition by jun proto-oncogene (JUN) of Sftpb promoter activity. In transient cotransfection assays, JUN inhibited the luciferase reporter activity of plasmid constructs containing Sftpb promoter fragments that lacked the distal putative AP-1 site, indicating that another regulatory motif mediates JUN-dependent inhibition. Electrophoretic mobility shift assays and in silico analyses identified a DNA target sequence (Sftpb nucleotides -339 to -316) and transcription factors that regulate Sftpb promoter activity. The identified sequence contains a CCAAT/enhancer-binding protein (C/EBP) consensus recognition element. Mutation of the site reduced Sftpb promoter activity and sensitivity to inhibition by JUN. Purified recombinant JUN, which did not recognize the -339 to -316 target sequence when added alone, supershifted the mobility of in vitro translated C/EBP-alpha and C/EBP-beta proteins complexed with the identified cis-regulatory element. These findings support the idea that heterodimerization between JUN and C/EBP-alpha and/or C/EBP-beta targets JUN to the Sftpb promoter, thereby mediating its inhibitory regulatory role. |
