The LMO2/LDB1 macromolecular complex is critical in hematopoietic stem and progenitor cell specification and in the development of acute leukemia. This complex is comprised of core subunits of LMO2 and LDB1 as well as single-stranded DNA-binding protein (SSBP) cofactors and DNA-binding basic helix-loop-helix (bHLH) and GATA transcription factors. We analyzed the steady-state abundance and kinetic stability of LMO2 and its partners via Halo protein tagging in conjunction with variant proteins deficient in binding their respective direct protein partners. We discovered a hierarchy of protein stabilities (with half-lives in descending order) as follows: LDB1 > SSBP > LMO2 > TAL1. Importantly, LDB1 is a remarkably stable protein that confers enhanced stability upon direct and indirect partners, thereby nucleating the formation of the multisubunit protein complex. The data imply that free subunits are more rapidly degraded than those incorporated within the LMO2/LDB1 complex. Our studies provided significant insights into LMO2/LDB1 macromolecular protein complex assembly and stability, which has implications for understanding its role in blood cell formation and for therapeutically targeting this complex in human leukemias.

中文翻译：

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LDB1增强白血病中直接和间接癌蛋白伴侣的稳定性。

LMO2 / LDB1大分子复合物在造血干细胞和祖细胞规格以及急性白血病的发展中至关重要。该复合物由LMO2和LDB1的核心亚基以及单链DNA结合蛋白（SSBP）辅助因子和DNA结合基本螺旋-环-螺旋（bHLH）和GATA转录因子组成。我们分析了LMO2及其伙伴通过Halo蛋白标记与不足以结合其各自直接蛋白伴侣的变体蛋白结合在一起的稳态丰度和动力学稳定性。我们发现蛋白质稳定性的层次结构（半衰期按降序排列）如下：LDB1> SSBP> LMO2> TAL1。重要的是，LDB1是一种非常稳定的蛋白质，可赋予直接和间接伙伴增强的稳定性，从而成核了多亚基蛋白质复合物的形成。数据表明，游离亚基的降解速度要快于LMO2 / LDB1复合物中的亚基。我们的研究为LMO2 / LDB1大分子蛋白质复合物的组装和稳定性提供了重要的见识，这对于理解其在血细胞形成中的作用以及在人类白血病中治疗性靶向该复合物具有重要意义。