Curtiss J, Heilig J S
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309-0347, USA.
Bioessays. 1998 Jan;20(1):58-69. doi: 10.1002/(SICI)1521-1878(199801)20:1<58::AID-BIES9>3.0.CO;2-O.
LIM-homeodomain transcription factors (LIM-HD) regulate expression of genes that pattern the body and generate cell specificity during development in invertebrates and vertebrates. It is especially interesting that most are expressed in and participate in the development of the nervous system. LIM-HD proteins are themselves regulated by both intramolecular and intermolecular interactions mediated by the LIM domains. LIM domains positively regulate LIM-HD activity by promoting protein-protein interactions that allow cooperative binding to regulatory regions of tissue-specific promoters. They also negatively regulate LIM-HD activity, possibly by preventing HD association with DNA. Interaction of LIM domains with other proteins relieves this interference, permitting DNA binding and providing a mechanism for refining LIM-HD activity. The recurrence of LIM-HD proteins in fundamental developmental processes emphasizes the importance of their function and regulation and provides an opportunity to identify mechanisms and molecules underlying patterning and cell specification.
LIM 同源结构域转录因子(LIM-HD)调控着在无脊椎动物和脊椎动物发育过程中决定身体模式并产生细胞特异性的基因的表达。特别有趣的是,大多数 LIM-HD 转录因子在神经系统中表达并参与其发育。LIM-HD 蛋白自身受到由 LIM 结构域介导的分子内和分子间相互作用的调控。LIM 结构域通过促进蛋白质-蛋白质相互作用来正向调节 LIM-HD 的活性,这种相互作用允许其协同结合到组织特异性启动子的调控区域。它们也可能通过阻止同源结构域(HD)与 DNA 的结合来负向调节 LIM-HD 的活性。LIM 结构域与其他蛋白质的相互作用可消除这种干扰,使 DNA 能够结合,并提供了一种优化 LIM-HD 活性的机制。LIM-HD 蛋白在基本发育过程中的反复出现强调了其功能和调控的重要性,并为识别模式形成和细胞特化背后的机制和分子提供了契机。