研究动态
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Spt5 与 Myc 存在遗传相互作用,并限制果蝇脑肿瘤的生长。

Spt5 interacts genetically with Myc and is limiting for brain tumor growth in Drosophila.

发表日期:2024 Jan
作者: Julia Hofstetter, Ayoola Ogunleye, André Kutschke, Lisa Marie Buchholz, Elmar Wolf, Thomas Raabe, Peter Gallant
来源: Brain Structure & Function

摘要:

转录因子 SPT5 与 MYC 癌蛋白发生物理相互作用,对于培养细胞中 MYC 靶标的有效转录激活至关重要。在这里,我们使用果蝇来解决这种相互作用在生物体中的相关性。 Spt5 在快速增殖的年轻成虫盘细胞中与 Myc 表现出适度的协同作用。在后来的发育过程中,Spt5 敲低本身没有可检测到的后果,但会强烈增强 Myc 过度表达引起的眼睛缺陷。同样,幼虫2型神经母细胞中的Spt5敲低对对照果蝇的大脑发育和存活仅产生轻微影响,但显着缩小了实验诱导的神经母细胞肿瘤的体积,并显着延长了荷瘤动物的寿命。当 Spt5 被系统性敲除以及肿瘤发生后,这种有益效果仍然可以观察到,这凸显了 SPT5 作为人类肿瘤学中的潜在药物靶点。© 2023 Hofstetter 等人。
The transcription factor SPT5 physically interacts with MYC oncoproteins and is essential for efficient transcriptional activation of MYC targets in cultured cells. Here, we use Drosophila to address the relevance of this interaction in a living organism. Spt5 displays moderate synergy with Myc in fast proliferating young imaginal disc cells. During later development, Spt5-knockdown has no detectable consequences on its own, but strongly enhances eye defects caused by Myc overexpression. Similarly, Spt5-knockdown in larval type 2 neuroblasts has only mild effects on brain development and survival of control flies, but dramatically shrinks the volumes of experimentally induced neuroblast tumors and significantly extends the lifespan of tumor-bearing animals. This beneficial effect is still observed when Spt5 is knocked down systemically and after tumor initiation, highlighting SPT5 as a potential drug target in human oncology.© 2023 Hofstetter et al.