Regulation of apoptosis of rbf mutant cells during Drosophila development.
Regulation of apoptosis of rbf mutant cells during Drosophila development.
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DOI：
10.1016/j.ydbio.2008.11.035
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发表时间：
2009-02-15
影响因子：
2.7
通讯作者：
Du, Wei
中科院分区：
文献类型：
--
作者：
Tanaka-Matakatsu, Miho;Xu, Jinhua;Cheng, Leping;Du, Wei
视网膜母细胞瘤基因Rb的失活导致细胞增殖、分化或凋亡的缺陷，这取决于特定的细胞或组织类型。为了深入了解可以调节Rb失活后果的基因，我们在果蝇中进行了基因筛选，以确定影响视网膜母细胞瘤家族蛋白（rbf）失活诱导的细胞凋亡的突变，并确定了一个阻止rbf诱导的细胞凋亡的突变。我们发现这个突变是头对合缺陷（head involution defective, hid）的一个新的等位基因，并且在rbf突变细胞中，hid的表达被解除了。我们发现了一种可以调节hid表达的增强子，它可以响应发育线索和辐射，并证明这种hid增强子通过E2F结合位点被RBF直接抑制。这些观察结果表明，rbf突变细胞的凋亡是由hid的上调介导的。最后，研究人员发现，调节hid翻译的miRNA bantam在幼虫眼盘的间细胞中表达，并调节rbf突变细胞的存活。
Inactivation of the retinoblastoma gene Rb leads to defects in cell proliferation, differentiation, or apoptosis, depending on specific cell or tissue types. To gain insights into the genes that can modulate the consequences of Rb inactivation, we carried out a genetic screen in Drosophila to identify mutations that affected apoptosis induced by inactivation of the Retinoblastoma-family protein (rbf) and identified a mutation that blocked apoptosis induced by rbf. We found this mutation to be a new allele of head involution defective (hid) and showed that hid expression is deregulated in rbf mutant cells in larval imaginal discs. We identified an enhancer that regulates hid expression in response to developmental cues as well as to radiation and demonstrated that this hid enhancer is directly repressed by RBF through an E2F binding site. These observations indicate that apoptosis of rbf mutant cells is mediated by an upregulation of hid. Finally, we showed that bantam, a miRNA that regulates hid translation, is expressed in the interommatidial cells in the larval eye discs and modulates the survival of rbf mutant cells.
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