Drosophila myeloid leukemia factor acts with DREF to activate the JNK signaling pathway.
Drosophila myeloid leukemia factor acts with DREF to activate the JNK signaling pathway.
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DOI：
10.1038/oncsis.2014.13
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发表时间：
2014-04-21
期刊：
影响因子：
6.2
通讯作者：
Yamaguchi, M.
中科院分区：
文献类型：
--
作者：
Yanai, H.;Yoshioka, Y.;Yoshida, H.;Nakao, Y.;Plessis, A.;Yamaguchi, M.
果蝇骨髓发育不良/髓系白血病因子(DMLF)是人类MLF1癌基因的同源物，首次以DNA复制相关元件结合因子(DREF)为诱饵，通过酵母双杂交筛选鉴定。DREF是一种转录因子，调节果蝇的增殖相关基因。已知dMLF通过Engrailed-GAL4驱动器在翼状成像盘中过表达，导致与诱导细胞凋亡相关的翼状萎缩表型。然而，所涉及的确切机制尚不清楚。在这里，我们发现果蝇Jun氨基末端激酶(JNK)篮子(BSK)的功能缺失突变抑制了萎缩的表型。在Puckered-LacZ报告线监测的翼盘中，过表达dMLF诱导了异位JNK激活，从而诱导了细胞凋亡。可以证明BSK启动子中存在与DREF结合的共识DRE序列。用抗dMLF-Ig G和实时荧光定量聚合酶链式反应对S2细胞进行染色质免疫沉淀分析，发现dMLF与含有DRE序列的bsk启动子区域特异性结合。此外，使用瞬时荧光素酶表达分析，我们提供了证据，敲除dMLF降低了S2细胞中bsk基因启动子的活性。最后，我们在体内证明了dMLF与DREF的相互作用。综上所述，这些数据表明，dMLF与DREF一起作用于BSK启动子，从而激活JNK途径促进细胞凋亡。
Drosophila myelodysplasia/myeloid leukemia factor (dMLF), a homolog of human MLF1, oncogene was first identified by yeast two-hybrid screen using the DNA replication-related element-binding factor (DREF) as bait. DREF is a transcription factor that regulates proliferation-related genes in Drosophila. It is known that overexpression of dMLF in the wing imaginal discs through the engrailed-GAL4 driver causes an atrophied wing phenotype associated with the induction of apoptosis. However, the precise mechanisms involved have yet to be clarified. Here, we found the atrophied phenotype to be suppressed by loss-of-function mutation of Drosophila Jun N-terminal kinase (JNK), basket (bsk). Overexpression of dMLF induced ectopic JNK activation in the wing disc monitored with the puckered-lacZ reporter line, resulting in induction of apoptosis. The DREF-binding consensus DRE sequence could be shown to exist in the bsk promoter. Chromatin immunoprecipitation assays in S2 cells with anti-dMLF IgG and quantitative real-time PCR revealed that dMLF binds specifically to the bsk promoter region containing the DRE sequence. Furthermore, using a transient luciferase expression assay, we provide evidence that knockdown of dMLF reduced bsk gene promoter activity in S2 cells. Finally, we show that dMLF interacts with DREF in vivo. Altogether, these data indicate that dMLF acts with DREF to stimulate the bsk promoter and consequently activates the JNK pathway to promote apoptosis.
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DOI：
10.1083/jcb.107.5.1629
发表时间：
1988-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Feuerstein N;Spiegel S;Mond JJ
通讯作者：
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DOI：
10.1016/j.bbaexp.2006.07.002
发表时间：
2006-07-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
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作者：
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DOI：
10.1073/pnas.97.14.7888
发表时间：
2000-07-05
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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