Regulation of the vav proto-oncogene by LKLF.
Regulation of the vav proto-oncogene by LKLF.
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LKLF 对 vav 原癌基因的调节。
DOI：
10.1016/s0378-1119(01)00792-2
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发表时间：
2001
期刊：
影响因子：
3.5
通讯作者：
Kawahara,RS
中科院分区：
文献类型：
--
作者：
Denkinger,DJ;Cushman-Vokoun,AM;Kawahara,RS
VaV原癌基因的转录诱导与确定的造血干细胞第一次出现在主动脉-性腺-中肾区域是一致的。Vav启动子的活性依赖于先前发现的含有PU.1和RUNX1/AML-1结合位点的23bpDNA片段和新发现的高度保守的12bpDNA片段(B框)。B盒的序列在人类、小鼠和大鼠中是相同的。CACCC核心序列的突变导致VaV启动子活性降低。在造血细胞中发现了与B盒结合的蛋白复合体，而在不表达VaV的细胞中未发现该复合体。含有CACCC核心突变的双链寡核苷酸在电迁移率变化分析竞争中的效率低于野生型序列。紫外光交联研究发现U937细胞中有一个37 kDa的DNA结合蛋白与B盒相互作用。抗体超转移实验证实该蛋白为肺Krüppel样因子(LKLF)。表达为谷胱甘肽S-转移酶融合蛋白的LKLF能与B盒结合。显性负性LKLF能抑制VaV启动子增强的绿色荧光蛋白的表达，染色质免疫沉淀检测到LKLF与VaV启动子结合，但不能与HeLa细胞结合。这些体外结果表明，未来将进行体内实验，以检验LKLF在从血管内皮细胞形成最终的造血干细胞过程中诱导VaV的作用。LKLF是血管生成所需的基因。
The transcriptional induction of the vav proto-oncogene coincides with the first appearance of the definitive hematopoietic stem cell in the aorta-gonad-mesonephros region. Vav promoter activity was dependent on a previously identified 23 bp DNA segment containing PU.1 and Runx1/AML-1 binding sites and on a newly identified, highly conserved, 12 bp DNA segment (Box B). The sequence of Box B was identical in the human, mouse and rat species. Mutation of the CACCC core sequence led to diminished vav promoter activity. A protein complex which bound to Box B was found in hematopoietic cells but not in cells which did not express vav. A double-stranded oligonucleotide containing a mutation of the CACCC core was less effective in electro-mobility shift assay competitions than the wild-type sequence. UV crosslinking studies identified a 37 kDa DNA binding protein which interacted with Box B in U937 cells. Antibody supershift assays identified this protein as lung Krüppel-like factor (LKLF). LKLF, expressed as a glutathione S-transferase fusion protein, was capable of binding to Box B. A dominant-negative LKLF was able to inhibit the expression of enhanced green fluorescent protein by the vav promoter and chromatin immunoprecipitations detected LKLF bound to the vav promoter in U937 but not HeLa cells. These in vitro results suggest future in vivo experiments to examine the role of LKLF, a gene required for vasculogenesis, in the induction of vav during the genesis of the definitive hematopoietic stem cell from the vascular endothelium.
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影响因子：
4.8
作者：
Romero, F;Fischer, S
通讯作者：
Fischer, S
缺乏 vav 原癌基因的淋巴细胞中 T 细胞和 B 细胞抗原受体的信号传导缺陷
影响因子：
64.8
作者：
Rong Zhang;F. Alt;L. Davidson;S. Orkin;W. Swat
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W. Swat
影响因子：
20.3
作者：
S. Ogilvy;Donald Metcalf;L. Gibson;M. Bath;A. W. Harris;Jerry M. Adams
通讯作者：
S. Ogilvy;Donald Metcalf;L. Gibson;M. Bath;A. W. Harris;Jerry M. Adams
影响因子：
8
作者：
Okada, H;Watanabe, T;Satake, M
通讯作者：
Satake, M
影响因子：
11.4
作者：
KATZAV, S;MARTINZANCA, D;BARBACID, M
通讯作者：
BARBACID, M