Myocardin-related transcription factor A (MRTF-A) (MRTF-A)

Myocardin-related transcription factor A (MRTF-A), also known as MKL1, is a transcriptional co-activator that plays a pivotal role in linking cytoskeletal dynamics to gene expression (UniProt Q969H0). It is sequestered in the cytoplasm through its N-terminal RPEL motifs binding to monomeric G-actin; upon Rho-GTPase activation and subsequent actin polymerization, MRTF-A is released and translocates to the nucleus via its N-terminal basic domain/nuclear localization signal (NLS) (PMID: 12832491). In the nucleus, it associates with Serum Response Factor (SRF) to drive the transcription of genes involved in cell motility, contractility, and myofibroblast differentiation (PMID: 24053230). This pathway is a key driver in fibrotic diseases, such as pulmonary and cardiac fibrosis, as well as in cancer metastasis and epithelial-mesenchymal transition (EMT) (PMID: 27535340). Therapeutic strategies focus on small molecule inhibitors, such as the CCG series (e.g., CCG-1423, CCG-203971), which target the N-terminal domain to block nuclear import and suppress pro-fibrotic gene programs (PMID: 24053230).

Other names

Megakaryoblastic leukemia 1 proteinMKL1MALBasic SAP and coiled-coil domain-containing proteinBSAC

Inhibition of nuclear translocation by targeting the N-terminal basic domain/nuclear localization signal (NLS) to prevent interaction with importin alpha/beta and subsequent SRF-mediated transcription (PMID: 24053230).