Identification of a cis-regulatory element and putative trans-acting factors responsible for 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated induction of heme oxygenase expression in myelomonocytic cell lines
Identification of a cis-regulatory element and putative trans-acting factors responsible for 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated induction of heme oxygenase expression in myelomonocytic cell lines
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鉴定负责 12-O-十四烷酰佛波醇-13-乙酸酯 (TPA) 介导的骨髓单核细胞系中血红素加氧酶表达诱导的顺式调节元件和推定的反式作用因子
DOI：
10.1128/mcb.13.12.7881-7891.1993
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发表时间：
1993
影响因子：
5.3
通讯作者：
Shigeki Shibahara
中科院分区：
文献类型：
--
作者：
Y. Muraosa;Shigeki Shibahara
人单核细胞白血病细胞系THP-1在用包括12-O-十四烷酰基佛波醇-13-乙酸酯（TPA）在内的多种试剂处理时分化成巨噬细胞样细胞。我们在这里表明，在这个过程中，血红素加氧酶的表达，在血红素催化剂的限速酶，诱导。用TPA处理也增加了其他骨髓单核细胞系中的血红素加氧酶mRNA，但在其他谱系的细胞系如HeLa细胞中不增加。血红素加氧酶活性增加可能代表活化的巨噬细胞的功能之一，其螯合衰老的红细胞并降解源自血红蛋白的血红素。TPA处理的这种细胞类型特异性诱导进一步研究了转录调控。我们在人血红素加氧酶基因的5 '侧翼区（-156 ~-147位）定义了一个顺式调控元件5'-GTCATATGAC-3 '，它在THP-1细胞中可被TPA诱导而在HeLa细胞中不被TPA诱导。在THP-1核提取物中鉴定了与该元件结合的核蛋白，其可能负责细胞特异性。该元件包含共有基序CANNTG，其与碱性螺旋-环-螺旋蛋白的大家族结合。我们的研究结果表明，TPA介导的转录调控在骨髓单核细胞系的新机制。
The human monocytic leukemia cell line THP-1 differentiates into macrophage-like cells when treated with a variety of agents, including 12-O-tetradecanoylphorbol-13-acetate (TPA). We show here that during this process, the expression of heme oxygenase, a rate-limiting enzyme in heme catabolism, is induced. Treatment with TPA increases heme oxygenase mRNA in other myelomonocytic cell lines also, but not in cell lines of other lineages, such as HeLa cells. Increased heme oxygenase activity may represent one of the functions of activated macrophages, which sequestrate senescent erythrocytes and degrade heme derived from hemoglobin. This cell-type-specific induction by TPA treatment further investigated with respect to transcriptional regulation. We defined a cis-regulatory element, 5'-GTCATATGAC-3', located in the 5'-flanking region (positions -156 to -147) of the human heme oxygenase gene, which confers inducibility by TPA in THP-1 cells but not in HeLa cells. Nuclear proteins that bind to this element, which may be responsible for the cell specificity, were identified in THP-1 nuclear extracts. This element contains the consensus motif CANNTG, to which a large family of basic helix-loop-helix proteins binds. Our results suggest a novel mechanism of TPA-mediated transcriptional regulation in myelomonocytic cell lines.
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DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
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DOI：
10.1016/s0021-9258(18)37884-0
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DOI：
10.1172/jci111292
发表时间：
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期刊：
The Journal of clinical investigation
影响因子：
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作者：
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通讯作者：
Fanger,MW