研究动态
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核高迁移群A2(HMGA2)的相互作用组通过生物素邻近标记揭示。

Nuclear High Mobility Group A2 (HMGA2) Interactome Revealed by Biotin Proximity Labeling.

发表日期:2023 Feb 20
作者: Antoine Gaudreau-Lapierre, Thomas Klonisch, Hannah Nicolas, Thatchawan Thanasupawat, Laura Trinkle-Mulcahy, Sabine Hombach-Klonisch
来源: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

摘要:

非组蛋白染色质结合蛋白高迁移率族(AT)-钩蛋白2 (HMGA2) 在染色质重塑、基因组维护和保护中具有重要功能。 HMGA2 的表达在胚胎干细胞中最高,在细胞分化和衰老过程中下降,但在某些癌症中重新表达,其中高 HMGA2 表达通常与不良预后相吻合。 HMGA2 的核功能不能仅通过结合染色质来解释,而涉及到与其他蛋白质的复杂相互作用,其机理尚未完全理解。 本研究利用生物素近距标记,随后进行蛋白质组学分析,以识别 HMGA2 核相互作用伴侣。 我们测试了两种不同的生物素连接酶 HMGA2 构型(BioID2 和 miniTurbo),并发现已知和新的 HMGA2 相互作用伴侣,其功能主要在染色质生物学中。 这些 HMGA2 生物素连接酶融合构建物为相互作用组可发现研究提供了令人兴奋的新机会,可以在药物治疗期间监测核 HMGA2 相互作用组。
The non-histone chromatin binding protein High Mobility Group AT-hook protein 2 (HMGA2) has important functions in chromatin remodeling, and genome maintenance and protection. Expression of HMGA2 is highest in embryonic stem cells, declines during cell differentiation and cell aging, but it is re-expressed in some cancers, where high HMGA2 expression frequently coincides with a poor prognosis. The nuclear functions of HMGA2 cannot be explained by binding to chromatin alone but involve complex interactions with other proteins that are incompletely understood. The present study used biotin proximity labeling, followed by proteomic analysis, to identify the nuclear interaction partners of HMGA2. We tested two different biotin ligase HMGA2 constructs (BioID2 and miniTurbo) with similar results, and identified known and new HMGA2 interaction partners, with functionalities mainly in chromatin biology. These HMGA2 biotin ligase fusion constructs offer exciting new possibilities for interactome discovery research, enabling the monitoring of nuclear HMGA2 interactomes during drug treatments.