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Evidence for a Nuclear Role for Drosophila Dlg as a Regulator of the NURF Complex
Molecular Biology of the Cell ( IF 3.3 ) Pub Date : 2021-09-08 , DOI: 10.1091/mbc.e21-04-0187
Katherine A Sharp 1 , Mark J Khoury 1 , Frederick Wirtz-Peitz 2 , David Bilder 1
Affiliation  

Scrib, Dlg, and Lgl are basolateral regulators of epithelial polarity and tumor suppressors whose molecular mechanisms of action remain unclear. We used proximity biotinylation to identify proteins localized near Dlg in the Drosophila wing imaginal disc epithelium. In addition to expected membrane- and cytoskeleton-associated protein classes, nuclear proteins were prevalent in the resulting mass spectrometry data set, including all four members of the NURF chromatin remodeling complex. Subcellular fractionation demonstrated a nuclear pool of Dlg and proximity ligation confirmed its position near the NURF complex. Genetic analysis showed that NURF activity is also required for the overgrowth of dlg tumors, and this growth suppression correlated with a reduction in Hippo pathway gene expression. Together, these data suggest a nuclear role for Dlg in regulating chromatin and transcription through a more direct mechanism than previously thought.



中文翻译:

果蝇 Dlg 作为 NURF 复合物调节剂的核作用的证据

Scrib、Dlg 和 Lgl 是上皮极性的基底外侧调节因子和肿瘤抑制因子,其分子作用机制仍不清楚。我们使用邻近生物素化来识别定位在果蝇翼成虫盘上皮中 Dlg 附近的蛋白质。除了预期的膜和细胞骨架相关蛋白类别外,核蛋白在产生的质谱数据集中普遍存在,包括 NURF 染色质重塑复合物的所有四个成员。亚细胞分离证明了 Dlg 的核池,并且邻近结扎证实了其在 NURF 复合物附近的位置。遗传分析表明 NURF 活性也是dlg过度生长所必需的肿瘤,这种生长抑制与 Hippo 通路基因表达的减少相关。总之,这些数据表明 Dlg 通过比以前认为的更直接的机制调节染色质和转录的核作用。

更新日期:2021-09-09
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