Tanaka-Matakatsu Miho, Xu Jinhua, Cheng Leping, Du Wei
Ben May Department for Cancer Research, the University of Chicago, Chicago, IL 60637, USA.
Dev Biol. 2009 Feb 15;326(2):347-56. doi: 10.1016/j.ydbio.2008.11.035. Epub 2008 Dec 10.
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.
视网膜母细胞瘤基因Rb的失活会导致细胞增殖、分化或凋亡缺陷，具体取决于特定的细胞或组织类型。为了深入了解能够调节Rb失活后果的基因，我们在果蝇中进行了一项遗传筛选，以鉴定影响视网膜母细胞瘤家族蛋白（rbf）失活诱导的凋亡的突变，并鉴定出一个阻断rbf诱导凋亡的突变。我们发现这个突变是头部内卷缺陷（hid）的一个新等位基因，并表明hid在幼虫成虫盘的rbf突变细胞中表达失调。我们鉴定出一个增强子，它能响应发育信号以及辐射来调节hid的表达，并证明这个hid增强子通过一个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，我们表明，一种调节hid翻译的微小RNA bantam在幼虫眼盘中的小眼间细胞中表达，并调节rbf突变细胞的存活。
