Sevrioukov Evgueni A, Burr John, Huang Eric W, Assi Hikmat H, Monserrate Jessica P, Purves Dianne C, Wu Julie N, Song Eyun J, Brachmann Carrie Baker
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California 92697, USA.
Genesis. 2007 Apr;45(4):184-93. doi: 10.1002/dvg.20279.
Many developing tissues require programmed cell death (PCD) for proper formation. In mice and C. elegans, developmental PCD is regulated by the Bcl-2 family of proteins. Two bcl-2 genes are encoded in the Drosophila genome (debcl/dBorg1/Drob-1/dBok and buffy/dBorg2) and previous RNAi-based studies suggested a requirement for these in embryonic development. However, we report here that, despite the fact that many tissues in fruit flies are shaped by PCD, deletion of the bcl-2 genes does not perturb normal development. We investigated whether the fly bcl-2 genes regulate non-apoptotic processes that require caspases, but found these to be bcl-2 gene-independent. However, irradiation of the mutants demonstrates that DNA damage-induced apoptosis, mediated by Reaper, is blocked by buffy and that debcl is required to inhibit buffy. Our results demonstrate that developmental PCD regulation in the fly does not rely upon the Bcl-2 proteins, but that they provide an added layer of protection in the apoptotic response to stress.
许多正在发育的组织需要程序性细胞死亡（PCD）才能正常形成。在小鼠和秀丽隐杆线虫中，发育性PCD受Bcl-2蛋白家族调控。果蝇基因组中编码了两个bcl-2基因（debcl/dBorg1/Drob-1/dBok和buffy/dBorg2），之前基于RNA干扰的研究表明它们在胚胎发育中是必需的。然而，我们在此报告，尽管果蝇的许多组织是由PCD塑造的，但bcl-2基因的缺失并不会干扰正常发育。我们研究了果蝇的bcl-2基因是否调控需要半胱天冬酶的非凋亡过程，但发现这些过程与bcl-2基因无关。然而，对突变体进行辐射表明，由收割者介导的DNA损伤诱导的凋亡被buffy阻断，并且需要debcl来抑制buffy。我们的结果表明，果蝇中的发育性PCD调控并不依赖于Bcl-2蛋白，但它们在对应激的凋亡反应中提供了额外的保护层。
