Use of altered specificity mutants to probe a specific protein-protein interaction in differentiation:: The GATA-1:FOG complex
Use of altered specificity mutants to probe a specific protein-protein interaction in differentiation:: The GATA-1:FOG complex
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DOI：
10.1016/s1097-2765(00)80312-3
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发表时间：
1999-02-01
期刊：
影响因子：
16
通讯作者：
Orkin, SH
中科院分区：
文献类型：
--
作者：
Crispino, JD;Lodish, MB;Orkin, SH
GATA-1和FOG（GATA-1的朋友）对于红细胞和巨核细胞开发都是必不可少的。 Fog是一种锌指蛋白，与GATA-1的氨基（N）手指相互作用，并与GATA-1合作以促进分化。为了确定这种相互作用对于GATA-1的作用至关重要，我们选择了酵母中的GATA-1突变体，这些突变体无法与雾相互作用，但保留了正常的DNA结合，也是恢复相互作用的补偿雾突变体。这些新型的GATA-1突变体不会促进GATA-1（ - ）红细胞细胞的红系分化。第二站点雾突变体挽救了分化。因此，雾与GATA-1的相互作用对于GATA-1在红系分化中的功能至关重要。这些发现为剖析参与哺乳动物发育的蛋白质 - 蛋白质关联提供了范式。
GATA-1 and FOG (Friend of GATA-1) are each essential for erythroid and megakaryocyte development. FOG, a zinc finger protein, interacts with the amino (N) finger of GATA-1 and cooperates with GATA-1 to promote differentiation. To determine whether this interaction is critical for GATA-1 action, we selected GATA-1 mutants in yeast that fail to interact with FOG but retain normal DNA binding, as well a compensatory FOG mutant that restores interaction. These novel GATA-1 mutants do not promote erythroid differentiation of GATA-1(-) erythroid cells. Differentiation is rescued by the second-site FOG mutant. Thus, interaction of FOG with GATA-1 is essential for the function of GATA-1 in erythroid differentiation. These findings provide a paradigm for dissecting protein-protein associations involved in mammalian development.