Protein stability and transcription factor complex assembly determined by the SCL-LMO2 interaction
Protein stability and transcription factor complex assembly determined by the SCL-LMO2 interaction
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DOI：
10.1074/jbc.m703939200
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发表时间：
2007-11-16
影响因子：
4.8
通讯作者：
Hoang, Trang
中科院分区：
文献类型：
--
作者：
Lecuyer, Eric;Lariviere, Simon;Hoang, Trang
基因表达程序是由相互作用的转录因子网络建立的。碱性螺旋-环-螺旋因子SCL和仅LIM蛋白LMO 2是造血所必需的转录因子复合物的组分。在这里，我们表明，LMO 2和SCL是造血细胞中的主要相互作用伙伴，这种相互作用发生在通过一个保守的接口居住在环和螺旋2的SCL。这种相互作用使SCL复合物在DNA上的组装成核，并且是靶基因诱导和刺激红细胞和巨核细胞分化所需的。我们还表明，SCL确定造血细胞中的LMO 2蛋白水平，并揭示与SCL的相互作用防止LMO 2降解的蛋白酶体。我们建议，SCL-LMO 2相互作用耦合蛋白质稳定与更高阶的蛋白质复合物组装，从而提供了一个强大的手段，调节SCL复合物的化学计量和时空活动。这种相互作用可能在造血和白血病的转录控制中提供了限速步骤，并且类似的机制可以操作以控制不同蛋白质模块的组装。
Gene expression programs are established by networks of interacting transcription factors. The basic helix-loop-helix factor SCL and the LIM-only protein LMO2 are components of transcription factor complexes that are essential for hematopoiesis. Here we show that LMO2 and SCL are predominant interaction partners in hematopoietic cells and that this interaction occurs through a conserved interface residing in the loop and helix 2 of SCL. This interaction nucleates the assembly of SCL complexes on DNA and is required for target gene induction and for the stimulation of erythroid and megakaryocytic differentiation. We also demonstrate that SCL determines LMO2 protein levels in hematopoietic cells and reveal that interaction with SCL prevents LMO2 degradation by the proteasome. We propose that the SCL-LMO2 interaction couples protein stabilization with higher order protein complex assembly, thus providing a powerful means of modulating the stoichiometry and spatiotemporal activity of SCL complexes. This interaction likely provides a rate-limiting step in the transcriptional control of hematopoiesis and leukemia, and similar mechanisms may operate to control the assembly of diverse protein modules.