Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.
Genetics. 2010 May;185(1):189-98. doi: 10.1534/genetics.110.114975. Epub 2010 Feb 22.
The escort factor Scap is essential in mammalian cells for regulated activation of sterol regulatory element binding proteins (SREBPs). SREBPs are membrane-bound transcription factors. Cells lacking Scap cannot activate SREBP. They are therefore deficient in the transcription of numerous genes involved in lipid synthesis and uptake; they cannot survive in the absence of exogenous lipid. Here we report that, in contrast to mammalian cells, Drosophila completely lacking dscap are viable. Flies lacking dscap emerge at approximately 70% of the expected rate and readily survive as homozygous stocks. These animals continue to cleave dSREBP in some tissues. Transcription of dSREBP target genes in dscap mutant larvae is reduced compared to wild type. It is greater than in mutants lacking dSREBP and remains responsive to dietary lipids in dscap mutants. Flies lacking dscap do not require the caspase Drice to activate dSREBP. This contrasts with ds2p mutants. ds2p encodes a protease that releases the transcription factor domain of dSREBP from the membrane. Larvae doubly mutant for dscap and ds2p exhibit phenotypes similar to those of ds2p single mutants. Thus, dScap and dS2P, essential components of the SREBP activation machinery in mammalian cells, are dispensable in Drosophila owing to different compensatory mechanisms.
Scap 伴侣蛋白在哺乳动物细胞中对于固醇调节元件结合蛋白（SREBPs）的调节激活是必需的。SREBPs 是膜结合转录因子。缺乏 Scap 的细胞不能激活 SREBP。因此，它们在脂质合成和摄取所涉及的许多基因的转录中存在缺陷；它们在没有外源性脂质的情况下无法存活。在这里，我们报告说，与哺乳动物细胞相反，完全缺乏 dscap 的果蝇是有活力的。缺乏 dscap 的果蝇以大约预期的 70%的速度出现，并容易作为纯合品系存活。这些动物在某些组织中继续切割 dSREBP。与野生型相比，dscap 突变体幼虫中 dSREBP 靶基因的转录减少。它大于缺乏 dSREBP 的突变体，并在 dscap 突变体中仍然对膳食脂质有反应。缺乏 dscap 的果蝇不需要 caspase Drice 来激活 dSREBP。这与 ds2p 突变体形成对比。ds2p 编码一种蛋白酶，将 dSREBP 的转录因子结构域从膜上释放出来。dscap 和 ds2p 双突变体幼虫表现出与 ds2p 单突变体相似的表型。因此，dScap 和 dS2P，哺乳动物细胞中 SREBP 激活机制的必需组成部分，由于不同的补偿机制，在果蝇中是可有可无的。
