Myocardin-related transcription factor (MRTF)

RPEL proteins, primarily comprising Myocardin-related transcription factors A and B (MRTF-A/B) and Myocardin, are characterized by the presence of conserved Arg-Pro-Glu-Leu (RPEL) motifs that function as sensors for globular actin (G-actin) (UniProt: Q96NR8, Q9ULH7). These proteins act as transcriptional coactivators that link cytoskeletal dynamics to gene expression by responding to changes in the ratio of G-actin to filamentous actin (F-actin) (PubMed: 15107404). When G-actin levels are high, it binds to the RPEL motifs and sequesters the MRTFs in the cytoplasm; conversely, actin polymerization releases MRTFs, allowing them to translocate to the nucleus and activate Serum Response Factor (SRF)-dependent transcription (PubMed: 23345435). This pathway is a critical driver of the myofibroblast phenotype in fibrotic diseases and promotes the epithelial-mesenchymal transition (EMT) and invasive behavior in cancer cells (PubMed: 28213349). Therapeutic targeting of RPEL proteins involves small molecules like CCG-1423 and CCG-203971, which aim to inhibit MRTF nuclear translocation or disrupt the MRTF-SRF interaction to treat fibrosis and prevent metastasis (PubMed: 24401039).

Other names

MRTF-AMRTF-BMKL1MKL2MALMegakaryoblastic leukemia 1RPEL motif-containing proteins

Inhibition of MRTF nuclear translocation or disruption of the MRTF-SRF transcriptional complex (PubMed: 24401039).