School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.
Cells. 2024 Nov 17;13(22):1897. doi: 10.3390/cells13221897.
LC3 (microtubule-associated protein 1 light chain 3, called Atg8 in yeast and ) is one of the most well-studied autophagy-related proteins. LC3 controls the selectivity of autophagic degradation by interacting with LIR (LC3-interacting region) motifs also known as AIM (Atg8-interacting motifs) on selective autophagy receptors that carry cargo for degradation. Although the function of Atg8 family proteins is primarily cytoplasmic, they are also enriched in the nucleus. Despite the accumulating evidence indicating the presence of Atg8 proteins in the nucleus, the mechanisms by which they are targeted to the nucleus, their interactions with nuclear components, and their nuclear role in remain poorly understood. Here, we used yeast two-hybrid screening, and we identified transcription factor Deformed wings (Dwg) as an Atg8a-interacting protein in . Dwg-Atg8a interaction is LIR motif-dependent. We have created Dwg Y129A/I132A LIR mutant flies and shown that they exhibit elevated autophagy, improved resistance to oxidative stress, and starvation. Our results provide novel insights into the transcriptional regulation of autophagy in .
LC3（微管相关蛋白 1 轻链 3，在酵母中称为 Atg8）是研究最广泛的自噬相关蛋白之一。LC3 通过与选择性自噬受体上的 LIR（LC3 相互作用区域）基序（也称为 AIM（Atg8 相互作用基序））相互作用，控制自噬降解的选择性。虽然 Atg8 家族蛋白的功能主要在细胞质中，但它们也在核中富集。尽管越来越多的证据表明 Atg8 蛋白存在于核中，但它们被靶向到核中的机制、与核成分的相互作用以及它们在核中的作用在很大程度上仍不清楚。在这里，我们使用酵母双杂交筛选，鉴定出转录因子变形翅膀（Dwg）为酵母中的 Atg8a 相互作用蛋白。Dwg-Atg8a 相互作用依赖于 LIR 基序。我们已经创建了 Dwg Y129A/I132A LIR 突变果蝇，并表明它们表现出增强的自噬、提高的氧化应激和饥饿抗性。我们的结果为提供了自噬在中的转录调控的新见解。
