CCAAT-enhancer-binding proteins (C/EBP) regulate the tissue specific activity of the CD11c integrin gene promoter through functional interactions with Sp1 proteins
CCAAT-enhancer-binding proteins (C/EBP) regulate the tissue specific activity of the CD11c integrin gene promoter through functional interactions with Sp1 proteins
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DOI：
10.1074/jbc.272.46.29120
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发表时间：
1997-11-14
影响因子：
4.8
通讯作者：
Corbi, AL
中科院分区：
文献类型：
--
作者：
LopezRodriguez, C;Botella, L;Corbi, AL
CD 11 c/CD 18整合素结合脂多糖、纤维蛋白原和肝素，并介导白细胞粘附、扩散和迁移。CD 11 c/CD 18主要存在于髓系细胞上，其表达在髓系分化过程中通过作用于CD 11 c基因启动子的转录机制调节。CD 11 c启动子的组织特异性和发育调节活性，CD 11 c启动子内的C/EBP结合位点（CEBP-80）在未分化的U937细胞中被CEBP α结合，在佛波醇12-肉豆蔻酸酯13-乙酸酯分化细胞中被含有C/EBP α和C/EBP β的二聚体结合，并且其破坏以细胞类型依赖性方式降低CD 11 c启动子活性，C/EBP α通过CEBP-80元件反式激活CD 11 c启动子，并且C/EBP α反式激活也依赖于Sp1-70-和Sp1-120 Spl结合位点。来自CD 11 c启动子的-90/-50片段，含有相邻的CEBP-80、Sp1-70和AP 1 -60位点，差异性地增强造血细胞和上皮细胞中最小催乳素启动子的活性。总之，这些结果表明C/EBP因子通过与Sp1的功能性相互作用参与CD 11 c/CD 18整联蛋白的组织限制性和调节性表达，表明Spl-related因子调节CD 11 c启动子上C/EBP α转录活性，并证明存在由C/EBP、Spl和AP-1因子识别的复合调节元件，其增强作用是细胞类型依赖性的。
The CD11c/CD18 integrin binds Lipopolysaccharide, fibrinogen, and heparin, and mediates leukocyte adhesion, spreading, and migration, CD11c/CD18 is primarily found on myeloid cells and its expression is regulated during myeloid differentiation by transcriptional mechanisms acting on the CD11c gene promoter, We now describe that CCAAT/enhancer-binding proteins (C/EBP) contribute to the basal. tissue-specific and developmentally regulated activity of the CD11c promoter, A C/EBP-binding site within the CD11c promoter (CEBP-80) is bound by CEBP alpha in undifferentiated U937 cells and by C/EBP alpha- and C/EBP beta-containing dimers in phorbol 12-myristate 13-acetate-differentiating cells, and its disruption decreased the CD11c promoter activity in a cell type-dependent manner, C/EBP alpha transactivated the CD11c promoter through the CEBP-80 element, and C/EBP alpha transactivation was also dependent on the Sp1-70- and Sp1-120 Spl binding sites. The -90/-50 fragment from the CD11c promoter, containing the adjacent CEBP-80, Sp1-70, and AP1-60 sites, differentially enhanced the activity of the minimal prolactin promoter in hematopoietic and epithelial cells, Altogether, these results demonstrate that C/EBP factors participate in the tissue-restricted and regulated expression of the CD11c/CD18 integrin through functional interactions with Sp1, suggest that Spl-related factors modulate C/EBP alpha transcriptional activity on the CD11c promoter, and demonstrate the existence of a composite regulatory element recognized by C/EBP, Spl, and AP-1 factors and whose enhancing effects are cell-type dependent.