Compensatory proliferation in Drosophila imaginal discs requires Dronc-dependent p53 activity.
Compensatory proliferation in Drosophila imaginal discs requires Dronc-dependent p53 activity.
复制标题
果蝇成虫盘的代偿性增殖需要 Dronc 依赖性 p53 活性。
DOI：
10.1016/j.cub.2006.07.046
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Johnston,LauraA
中科院分区：
文献类型：
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作者：
Wells,BrentS;Yoshida,Eri;Johnston,LauraA
背景 p53 转录因子指导转录程序，决定细胞在 DNA 损伤后是否存活或死亡。动物在广泛的细胞损伤后生存通常需要通过补偿性生长或再生来替换丢失的组织。在果蝇中，受损的成虫盘细胞可以诱导邻近活细胞的增殖，但如何控制这种情况尚不清楚。在这里，我们提供的证据表明，果蝇53 (dp53)在协调对组织损伤的代偿性生长反应中具有先前未识别的作用。结果我们发现，果蝇中唯一的p53直系同源物dp53是对细胞损伤反应的每个组成部分所必需的，包括两个独立的细胞周期停滞、模式基因表达的变化、细胞增殖和生长。我们证明这些过程由 dp53 以独立于 DNA 损伤传感的方式调节，但需要启动子 caspase Dronc。我们的结果表明，一旦被诱导，dp53 就会通过与 Dronc 以及细胞凋亡诱导因子 Hid 和 Reaper 形成的正反馈环路来放大和维持反应。 结论 在发育过程中和应激后如何协调细胞死亡和细胞增殖是一个基本问题，对于理解生长调节至关重要。我们的数据表明，dp53 可能执行一种祖先功能，通过协调组织损伤后的补偿性生长反应来促进动物生存。
BackgroundThe p53 transcription factor directs a transcriptional program that determines whether a cell lives or dies after DNA damage. Animal survival after extensive cellular damage often requires that lost tissue be replaced through compensatory growth or regeneration. InDrosophila, damaged imaginal disc cells can induce the proliferation of neighboring viable cells, but how this is controlled is not clear. Here we provide evidence thatDrosophilap53 (dp53) has a previously unidentified role in coordinating the compensatory growth response to tissue damage.ResultsWe find that dp53, the sole p53 ortholog inDrosophila, is required for each component of the response to cellular damage, including two separate cell-cycle arrests, changes in patterning gene expression, cell proliferation, and growth. We demonstrate that these processes are regulated by dp53 in a manner that is independent of DNA-damage sensing but that requires the initiator caspase Dronc. Our results indicate that once induced, dp53 amplifies and sustains the response through a positive feedback loop with Dronc and the apoptosis-inducing factors Hid and Reaper.ConclusionsHow cell death and cell proliferation are coordinated during development and after stress is a fundamental question that is critical for an understanding of growth regulation. Our data suggest that dp53 may carry out an ancestral function that promotes animal survival through the coordination of responses leading to compensatory growth after tissue damage.