{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMyocardin‐related transcription factor A (MRTFA, also known as MKL1 or MAL) is a RhoA‐actin–regulated transcriptional coactivator of serum response factor (SRF) that couples cytoskeletal dynamics to gene expression. Under basal conditions, MRTFA resides in the cytoplasm through its interaction with globular actin via conserved RPEL motifs, and signals that promote actin polymerization (or post‐translational modifications such as ERK1/2‐mediated phosphorylation) trigger its nuclear translocation. In the nucleus, MRTFA binds SRF to drive the expression of immediate early, cytoskeletal, and muscle‐specific genes that regulate cell adhesion, spreading, and motility. This fundamental signaling mechanism has been demonstrated in diverse cellular contexts, including tumor cells where MRTFA‐dependent transcription supports invasion and metastatic colonization, and in developing muscle and vascular cells where MRTFA activity facilitates differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMRTFA also plays a key role in cell fate decisions and pathologic conditions. It mediates transforming growth factor–β and BMP‐induced epithelial–mesenchymal transitions, smooth muscle and megakaryocytic differentiation, as well as the myofibroblast transition that underlies fibrotic remodeling. In cancer cells, tumor–promoting signals enhance MRTFA activity either alone or in concert with factors such as YAP or STAT3, thereby facilitating the expression of genes (for example, MYH9, MYL9, and collagen genes) that favor invasion, metastasis and even noncanonical Hedgehog pathway activation. Moreover, MRTFA’s capacity to interact with chromatin remodelers (e.g., via SMYD3) and its integration into complex gene‐regulatory circuits underscore a multifaceted role in both normal development and disease progression. Collectively, these studies identify MRTFA as a central mechanosensitive transcriptional regulator whose dysregulation underlies diverse pathological processes ranging from vascular and fibrotic disorders to cancer metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tomonari Sasazuki, Taisuke Sawada, Sachiko Sakon, et al. 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