Department of Biochemistry and Molecular Genetics University of Illinois at Chicago, 900 South Ashland Avenue, Chicago, IL 60607-7170, USA.
Dev Biol. 2012 Dec 1;372(1):88-102. doi: 10.1016/j.ydbio.2012.08.022. Epub 2012 Aug 29.
Successful development of a multicellular organism depends on the finely tuned orchestration of cell proliferation, differentiation and apoptosis from embryogenesis through adulthood. The MYB-gene family encodes sequence-specific DNA-binding transcription factors that have been implicated in the regulation of both normal and neoplastic growth. The Drosophila Myb protein, DMyb (and vertebrate B-Myb protein), has been shown to be part of the dREAM/MMB complex, a large multi-subunit complex, which in addition to four Myb-interacting proteins including Mip130, contains repressive E2F and pRB proteins. This complex has been implicated in the regulation of DNA replication within the context of chorion gene amplification and transcriptional regulation of a wide array of genes. Detailed phenotypic analysis of mutations in the Drosophila myb gene, Dm myb, has revealed a previously undiscovered function for the dREAM/MMB complex in regulating programmed cell death (PCD). In cooperation with the pro-apoptotic protein Grim and dREAM/MMB, DMyb promotes the PCD of specified sensory organ precursor daughter cells in at least two different settings in the peripheral nervous system: the pIIIb precursor of the neuron and sheath cells in the posterior wing margin and the glial cell in the thoracic microchaete lineage. Unlike previously analyzed settings, in which the main role of DMyb has been to antagonize the activities of other dREAM/MMB complex members, it appears to be the critical effector in promoting PCD. The finding that Dm myb and grim are both involved in regulating PCD in two distinct settings suggests that these two genes may often work together to mediate PCD.
多细胞生物的成功发育取决于胚胎发生到成年期细胞增殖、分化和凋亡的精细协调。MYB 基因家族编码序列特异性 DNA 结合转录因子,这些转录因子被认为参与正常和肿瘤生长的调节。果蝇 Myb 蛋白 DMyb(和脊椎动物 B-Myb 蛋白)已被证明是 dREAM/MMB 复合物的一部分,该复合物是一个大型多亚基复合物,除了包含四个与 Myb 相互作用的蛋白(包括 Mip130)外,还包含抑制性 E2F 和 pRB 蛋白。该复合物已被牵连到染色质基因扩增和广泛的基因转录调控的 DNA 复制的调节中。果蝇 myb 基因 Dm myb 的突变的详细表型分析揭示了 dREAM/MMB 复合物在调节程序性细胞死亡(PCD)中的一个以前未被发现的功能。在与促凋亡蛋白 Grim 和 dREAM/MMB 的合作下,DMyb 促进了至少两个不同的外周神经系统中特定感觉器官前体细胞的 PCD:神经元和鞘细胞的 pIIIb 前体以及胸部微刚毛谱系中的神经胶质细胞。与以前分析的设置不同,在这些设置中,DMyb 的主要作用是拮抗其他 dREAM/MMB 复合物成员的活性,它似乎是促进 PCD 的关键效应因子。发现 Dm myb 和 grim 都参与调节两个不同的 PCD 设置表明,这两个基因可能经常协同作用来介导 PCD。