Rath Nibedita, Wang Zhishan, Lu Min Min, Morrisey Edward E
Department of Medicine, University of Pennsylvania, Philadelphia, 19104, USA.
Mol Cell Biol. 2005 Oct;25(20):8864-73. doi: 10.1128/MCB.25.20.8864-8873.2005.
The activity of GATA factors is regulated, in part, at the level of protein-protein interactions. LIM domain proteins, first defined by the zinc finger motifs found in the Lin11, Isl-1, and Mec-3 proteins, act as coactivators of GATA function in both hematopoietic and cardiovascular tissues. We have identified a novel GATA-LIM interaction between GATA6 and LMCD1/dyxin. The LIM domains and cysteine-rich domains in LMCD1/dyxin and the carboxy-terminal zinc finger of GATA6 mediate this interaction. Expression of LMCD1/dyxin is remarkably similar to that of GATA6, with high-level expression observed in distal airway epithelium of the lung, vascular smooth muscle, and myocardium. In contrast to other GATA-LIM protein interactions, LMCD1/dyxin represses GATA6 activation of both lung and cardiac tissue-specific promoters. Electrophoretic mobility shift and chromatin immunoprecipitation assays show that LMCD1/dyxin represses GATA6 function by inhibiting GATA6 DNA binding. These data reveal an interaction between GATA6 and LMCD1/dyxin and demonstrate a novel mechanism through which LIM proteins can assert their role as transcriptional cofactors of GATA proteins.
GATA因子的活性部分在蛋白质-蛋白质相互作用水平受到调控。LIM结构域蛋白最初由在Lin11、Isl-1和Mec-3蛋白中发现的锌指基序所定义，在造血组织和心血管组织中作为GATA功能的共激活因子发挥作用。我们已经确定了GATA6与LMCD1/dyxin之间一种新的GATA-LIM相互作用。LMCD1/dyxin中的LIM结构域和富含半胱氨酸的结构域以及GATA6的羧基末端锌指介导了这种相互作用。LMCD1/dyxin的表达与GATA6的表达非常相似，在肺的远端气道上皮、血管平滑肌和心肌中观察到高水平表达。与其他GATA-LIM蛋白相互作用不同，LMCD1/dyxin抑制GATA6对肺和心脏组织特异性启动子的激活。电泳迁移率变动分析和染色质免疫沉淀分析表明，LMCD1/dyxin通过抑制GATA6与DNA的结合来抑制GATA6的功能。这些数据揭示了GATA6与LMCD1/dyxin之间的相互作用，并证明了一种新的机制，通过该机制LIM蛋白可以作为GATA蛋白的转录辅因子发挥作用。
