A SAGE approach to discovery of genes involved in autophagic cell death
A SAGE approach to discovery of genes involved in autophagic cell death
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DOI：
10.1016/s0960-9822(03)00082-4
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发表时间：
2003-02-18
期刊：
影响因子：
9.2
通讯作者：
Marra, MA
中科院分区：
文献类型：
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作者：
Gorski, SM;Chittaranjan, S;Marra, MA
程序性细胞死亡(PCD)在正常的动物生理和疾病中起重要作用，至少可分为两种形态亚型，包括I型(细胞凋亡)和II型(自噬细胞死亡[1])。在过去的十年里，许多与细胞凋亡有关的分子被发现并被深入研究，但自噬细胞死亡的分子特征还不是很好。在这里，我们首次全面鉴定了与体内正常后生动物发育过程中的自噬细胞死亡相关的分子。在果蝇变态期间，幼虫唾液腺经历自噬细胞死亡，受激素诱导的转录级联调节[2-6]。为了鉴定和分析表达的基因，我们使用基因表达系列分析(SAGE)检测了果蝇唾液腺死亡前三个阶段的野生型基因表达模式[7]。1244个转录本，包括与自噬、防御反应、细胞骨架重塑、非caspase蛋白分解和细胞凋亡相关的基因，在唾液腺死亡之前差异表达。突变表达分析表明，其中几个基因受e93调控，e93是唾液腺细胞死亡所必需的基因。我们的分析有力地支持了这一新兴概念，即涉及自噬细胞死亡和凋亡的分子存在重叠，也存在重要的差异。
Programmed cell death (PCD), important in normal animal physiology and disease, can be divided into at least two morphological subtypes, including type I, or apoptosis, and type II, or autophagic cell death [1]. While many molecules involved in apoptosis have been discovered and studied intensively during the past decade, autophagic cell death is not well characterized molecularly. Here we report the first comprehensive identification of molecules associated with autophagic cell death during normal metazoan development in vivo. During Drosophila metamorphosis, the larval salivary glands undergo autophagic cell death regulated by a hormonally induced transcriptional cascade [2-6]. To identify and analyze the genes expressed, we examined wild-type patterns of gene expression in three predeath stages of Drosophila salivary glands using serial analysis of gene expression (SAGE) [7]. 1244 transcripts, including genes involved in autophagy, defense response, cytoskeleton remodeling, noncaspase proteolysis, and apoptosis, were expressed differentially prior to salivary gland death. Mutant expression analysis indicated that several of these genes were regulated by E93, a gene required for salivary gland cell death [6]. Our analyses strongly support both the emerging notion that there is overlap with respect to the molecules involved in autophagic cell death and apoptosis, and that there are important differences.