Characterization of a tumor necrosis factor-responsive element which down-regulates the human osteocalcin gene.
Characterization of a tumor necrosis factor-responsive element which down-regulates the human osteocalcin gene.
复制标题
下调人骨钙素基因的肿瘤坏死因子反应元件的表征。
DOI：
10.1128/mcb.13.6.3714-3721.1993
复制
发表时间：
1993
影响因子：
5.3
通讯作者：
Stashenko,P
中科院分区：
文献类型：
--
作者：
Li,YP;Stashenko,P
Tumor necrosis factor (TNF) down-regulates the production of bone matrix proteins by osteoblasts, thereby inhibiting bone formation. Osteocalcin, the major noncollagenous protein in bone, is inhibited by TNF at the transcriptional level. Mapping studies were undertaken to characterize the TNF-responsive element (TNFRE) in the osteocalcin promoter. Deletion analysis localized the TNFRE to the -522/-511 region, which contains a 9-bp palindromic motif (AGGCTGCCT). Promoter segments containing this sequence down-regulated a heterologous simian virus 40 promoter. Site-specific mutagenesis of the TNFRE eliminated TNF down-regulation. Mobility shift assays demonstrated that a constitutively expressed nuclear factor bound to the TNFRE; this factor was tentatively identified as the p50 homodimer of NF-κB. TNF stimulation induced a second TNFRE-binding protein which displaced the constitutive factor. The TNF-induced protein was not inhibitable by the NF-κB consensus sequence and was unreactive with anti-NF-κ B antiserum. DNase footprinting demonstrated that both factors protected the -522/-501 portion of the promoter, consistent with the results of mapping studies and competitive mobility shift assays. It is hypothesized that the generalized catabolic activities of TNF in infectious and malignant diseases may be regulated via this novel element.
