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首页> 外文期刊>Molecular and Cellular Biology >Identification and Characterization of a Drosophila Proteasome Regulatory Network
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Identification and Characterization of a Drosophila Proteasome Regulatory Network

机译：果蝇蛋白酶体调控网络的鉴定和表征。

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Maintaining adequate proteasomal proteolytic activity is essential for eukaryotic cells. For metazoan cells, little is known about the composition of genes that are regulated in the proteasome network or the mechanisms that modulate the levels of proteasome genes. Previously, two distinct treatments have been observed to induce 26S proteasome levels in Drosophila melanogaster cell lines, RNA interference (RNAi)-mediated inhibition of the 26S proteasome subunit Rpn10/S5a and suppression of proteasome activity through treatment with active-site inhibitors. We have carried out genome array profiles from cells with decreased Rpn10/S5a levels using RNAi or from cells treated with proteasome inhibitor MG132 and have thereby identified candidate genes that are regulated as part of a metazoan proteasome network. The profiles reveal that the majority of genes that were identified to be under the control of the regulatory network consisted of 26S proteasome subunits. The 26S proteasome genes, including three new subunits, Ubp6p, Uch-L3, and Sem1p, were found to be up-regulated. A number of genes known to have proteasome-related functions, including Rad23, isopeptidase T, sequestosome, and the genes for the segregase complex TER94/VCP-Ufd1-Npl4 were also found to be up-regulated. RNAi-mediated inhibition against the segregase complex genes demonstrated pronounced stabilization of proteasome substrates throughout the Drosophila cell. Finally, transcriptional reporter assays and deletion mapping studies in Drosophila demonstrate that proteasome mRNA induction is dependent upon the 5′ untranslated regions (UTRs). Transfer of the 5′ UTR from the proteasome subunit Rpn1/S2 to a noninducible promoter was sufficient to confer transcriptional upregulation of the reporter mRNA after proteasome inhibition.
机译：维持足够的蛋白酶体蛋白水解活性对于真核细胞至关重要。对于后生细胞，对蛋白酶体网络中调节的基因组成或调节蛋白酶体基因水平的机制知之甚少。以前，已经观察到两种不同的治疗方法可在果蝇（Drosophila melanogaster）细胞系中诱导26S蛋白酶体水平，RNA干扰（RNAi）介导的对26S蛋白酶体亚基Rpn10 / S5a的抑制作用以及通过蛋白酶处理抑制蛋白酶体活性。活性部位抑制剂。我们已经使用RNAi从Rpn10 / S5a水平降低的细胞或经蛋白酶体抑制剂MG132处理的细胞中进行了基因组阵列分析，从而鉴定了作为后生蛋白酶体网络一部分受到调控的候选基因。这些图谱表明，被鉴定为处于调控网络控制之下的大多数基因均由26S蛋白酶体亚基组成。发现26S蛋白酶体基因，包括三个新的亚基Ubp6p，Uch-L3和Sem1p，被上调。还发现许多已知具有蛋白酶体相关功能的基因，包括Rad23，异肽酶T，螯合体和segregase复合物TER94 / VCP-Ufd1-Npl4的基因均被上调。 RNAi介导的对segregase复杂基因的抑制作用表明在整个果蝇细胞中，蛋白酶体底物具有明显的稳定作用。最后，果蝇中的转录报告基因检测和缺失作图研究表明蛋白酶体mRNA的诱导依赖于5'非翻译区（UTRs）。从蛋白酶体亚基Rpn1 / S2到非诱导型启动子的5'UTR转移足以赋予蛋白酶体抑制后报告mRNA的转录上调。

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