Department of Laboratory Medicine, Yale School of Medicine, New Haven, Connecticut, USA; Yale Stem Cell Center, Yale School of Medicine, New Haven, Connecticut, USA.
Yale Stem Cell Center, Yale School of Medicine, New Haven, Connecticut, USA; Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
J Biol Chem. 2021 Jan-Jun;296:100543. doi: 10.1016/j.jbc.2021.100543. Epub 2021 Mar 13.
Myocardin-related transcription factor A (MRTFA) is a coactivator of serum response factor, a transcription factor that participates in several critical cellular functions including cell growth and apoptosis. MRTFA couples transcriptional regulation to actin cytoskeleton dynamics, and the transcriptional targets of the MRTFA-serum response factor complex include genes encoding cytoskeletal proteins as well as immediate early genes. Previous work has shown that MRTFA promotes the differentiation of many cell types, including various types of muscle cells and hematopoietic cells, and MRTFA's interactions with other protein partners broaden its cellular roles. However, despite being first identified as part of the recurrent t(1;22) chromosomal translocation in acute megakaryoblastic leukemia, the mechanisms by which MRTFA functions in malignant hematopoiesis have yet to be defined. In this review, we provide an in-depth examination of the structure, regulation, and known functions of MRTFA with a focus on hematopoiesis. We conclude by identifying areas of study that merit further investigation.
肌球蛋白相关转录因子 A(MRTFA)是血清反应因子的共激活因子,该转录因子参与包括细胞生长和凋亡在内的几种关键细胞功能。MRTFA 将转录调控与肌动蛋白细胞骨架动力学偶联,MRTFA-血清反应因子复合物的转录靶标包括编码细胞骨架蛋白的基因和即刻早期基因。先前的研究表明,MRTFA 促进许多细胞类型的分化,包括各种类型的肌肉细胞和造血细胞,并且 MRTFA 与其他蛋白伴侣的相互作用扩展了其细胞作用。然而,尽管 MRTFA 最初被鉴定为急性巨核细胞白血病中反复出现的 t(1;22)染色体易位的一部分,但 MRTFA 在恶性造血中的功能机制尚未确定。在这篇综述中,我们深入研究了 MRTFA 的结构、调节和已知功能,重点是造血。最后,我们确定了值得进一步研究的领域。