Transforming acidic coiled-coil protein 3 (TACC3) controls friend of GATA-1 (FOG-1) subcellular localization and regulates the association between GATA-1 and FOG-1 during hematopoiesis
Transforming acidic coiled-coil protein 3 (TACC3) controls friend of GATA-1 (FOG-1) subcellular localization and regulates the association between GATA-1 and FOG-1 during hematopoiesis
复制标题
DOI：
10.1074/jbc.m313987200
复制
发表时间：
2004-05-28
影响因子：
4.8
通讯作者：
Orkin, SH
中科院分区：
文献类型：
--
作者：
Garriga-Canut, M;Orkin, SH
转录因子GATA-1和GATA-1的辅因子Friend of GATA-1(FOG-1)之间的物理结合对于红系细胞和巨核细胞这两种血细胞的分化是必不可少的。然而，关于它们在细胞内相互作用的调节机制，人们知之甚少。在本研究中，我们发现TACC3是一种与FOG-1相互作用的蛋白。转化酸性卷曲蛋白3(TACC3)是一种在造血细胞中高表达的蛋白，已被报道在未成熟造血祖细胞的扩增中起关键作用。我们发现TACC3影响FOG-1核定位，改变GATA-1和FOG-1之间的相互作用。然而，GATA-1在与FOG-1的相互作用中与TACC3竞争。我们观察到，高水平的TACC3抑制了FOG-1作为GATA-1的转录辅助因子的功能。此外，强迫表达TACC3到与祖细胞相似的水平会延迟MEL和G1ER细胞的最终成熟，这两个细胞模型是红系细胞发育的。我们建议TACC3在调节FOG-1的细胞分布中发挥作用，从而调节GATA-1和FOG-1的直接相互作用，作为一种机制来控制从多潜能祖细胞群体的扩张到红系成熟的最终阶段之间的过渡。
Physical association between the transcription factor GATA-1 and the cofactor, Friend of GATA-1 (FOG-1), is essential for the differentiation of two blood cell types, erythroid cells and megakaryocytes. However, little is known regarding the mechanisms that modulate their interaction within cells. In the present study, we have identified TACC3 as a FOG-1-interacting protein. Transforming acidic coiled-coil protein 3 ( TACC3), a protein that is highly expressed in hematopoietic cells, has been reported to have a critical role in the expansion of immature hematopoietic progenitors. We show that TACC3 affects FOG-1 nuclear localization, altering the interaction between GATA-1 and FOG-1. However, GATA-1 competes with TACC3 in the interaction with FOG-1. We observe that high levels of TACC3 inhibit the function of FOG-1 as a transcriptional cofactor of GATA-1. Furthermore, forced expression of TACC3 to levels similar to those found in progenitor cells delays terminal maturation of MEL and G1ER cells, two cell models of erythroid cell development. We suggest a role for TACC3 in regulating the cellular distribution of FOG-1 and thus the direct interaction of GATA-1 and FOG-1 as a mechanism to control the transition between expansion of multipotential progenitor cell populations and final stages of erythroid maturation.