Posern Guido, Treisman Richard
Department of Molecular Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Trends Cell Biol. 2006 Nov;16(11):588-96. doi: 10.1016/j.tcb.2006.09.008. Epub 2006 Oct 10.
The vast diversity of cellular types and behaviours is mainly the result of combinatorial interactions between a limited number of transcription factors and cellular signalling pathways whose activity is stringently controlled by developmental, cellular and extracellular cues. Studies of serum response factor (SRF) have provided a paradigm for such interactions for some years. Recent advances have shown that two families of SRF cofactors, the ternary complex factors (TCFs) and the myocardin-related transcription factors (MTRFs), are regulated by separate signalling pathways and thereby control SRF target genes differentially. The actin cytoskeleton is both an upstream regulator of MRTF activity, with monomeric actin directly acting as a signal transducer, and a downstream effector, because of the many cytoskeletal target genes. Here we discuss how the competition among cofactors might integrate these distinct signalling pathways into a specific transcriptional response and biological function.
细胞类型和行为的巨大多样性主要是有限数量的转录因子与细胞信号通路之间组合相互作用的结果,这些信号通路的活性受到发育、细胞和细胞外信号的严格控制。多年来,血清反应因子(SRF)的研究为这种相互作用提供了一个范例。最近的进展表明,SRF辅因子的两个家族,即三元复合因子(TCFs)和心肌相关转录因子(MTRFs),受不同的信号通路调控,从而差异地控制SRF靶基因。肌动蛋白细胞骨架既是MRTF活性的上游调节因子,单体肌动蛋白直接作为信号转导分子,又是下游效应器,因为存在许多细胞骨架靶基因。在这里,我们讨论了辅因子之间的竞争如何将这些不同的信号通路整合到特定的转录反应和生物学功能中。