| First Author | Kohda A | Year | 2014 |
| Journal | Genes Cells | Volume | 19 |
| Issue | 8 | Pages | 620-8 |
| PubMed ID | 24948478 | Mgi Jnum | J:230167 |
| Mgi Id | MGI:5755585 | Doi | 10.1111/gtc.12162 |
| Citation | Kohda A, et al. (2014) DNA element downstream of the kappaB site in the Lcn2 promoter is required for transcriptional activation by IkappaBzeta and NF-kappaB p50. Genes Cells 19(8):620-8 |
| abstractText | The nuclear protein IkappaBzeta activates transcription of a subset of NF-kappaB-dependent innate immune genes such as Lcn2 encoding the antibacterial protein lipocalin-2. IkappaBzeta functions as a coactivator via its interaction with NF-kappaB p50, which contains a DNA-binding Rel-homology domain but lacks a transcriptional activation domain. However cis-regulatory elements involved in IkappaBzeta function have remained unknown. Here, we show that, although IkappaBzeta by itself is unable to associate with the Lcn2 promoter, IkappaBzeta interacts with the promoter via p50 binding to the NF-kappaB-binding site (kappaB site) and the interaction also requires the pyrimidine-rich site (CCCCTC) that localizes seven bases downstream of the kappaB site. The pyrimidine-rich site is also essential for IkappaBzeta-mediated activation of the Lcn2 gene. Introduction of both sites into an IkappaBzeta-independent gene culminates in IkappaBzeta-p50-DNA complex formation and transcriptional activation. Furthermore, spacing between the two sites is crucial for both IkappaBzeta-DNA interaction and IkappaBzeta-mediated gene activation. Thus, the pyrimidine-rich IkappaBzeta-responsive site plays an essential role in productive interaction of IkappaBzeta with the p50-DNA complex. |
