Cakouros Dimitrios, Daish Tasman J, Mills Kathryn, Kumar Sharad
Hanson Institute, IMVS, Frome Road, Adelaide 5000, Australia.
J Biol Chem. 2004 Apr 30;279(18):18467-71. doi: 10.1074/jbc.M400972200. Epub 2004 Feb 19.
Developmentally programmed cell death is regulated by a balance between pro- and anti-death signaling. During Drosophila metamorphosis, the removal of larval tissues is dependent on the steroid hormone ecdysone, which controls the levels of pro- and anti-death molecules. Ecdysone binds to its heterodimeric receptor ecdysone receptor/ultraspiracle to mediate transcription of primary response genes. Here we show that CARMER, an arginine-histone methyltransferase, is critical in coordinating ecdysone-induced expression of Drosophila cell death genes. Ablation of CARMER blocks ecdysone-induced cell death in Drosophila cells, but not apoptosis induced by cell stress. We demonstrate that CARMER associates with the ecdysone receptor complex and modulates the ecdysone-induced transcription of a number of apoptotic genes. Thus, the chromatin-modifying protein, CARMER, modulates cell death by controlling the hormone-dependent expression of the core cell death machinery.
发育程序性细胞死亡受促死亡信号和抗死亡信号之间平衡的调控。在果蝇变态发育过程中，幼虫组织的清除依赖于类固醇激素蜕皮激素，它控制着促死亡分子和抗死亡分子的水平。蜕皮激素与其异源二聚体受体蜕皮激素受体/超气门蛋白结合，介导初级反应基因的转录。在此我们表明，精氨酸 - 组蛋白甲基转移酶CARMER在协调蜕皮激素诱导的果蝇细胞死亡基因表达中起关键作用。敲除CARMER可阻断果蝇细胞中蜕皮激素诱导的细胞死亡，但不影响细胞应激诱导的凋亡。我们证明CARMER与蜕皮激素受体复合物相关联，并调节蜕皮激素诱导的多个凋亡基因的转录。因此，染色质修饰蛋白CARMER通过控制核心细胞死亡机制的激素依赖性表达来调节细胞死亡。
