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

Myocardin-related transcription factor B (MRTF-B), encoded by the MKL2 gene, is a transcriptional coactivator that plays a pivotal role in regulating genes associated with the actin cytoskeleton and smooth muscle cell identity [UniProt: Q9ULH7]. It functions primarily by binding to Serum Response Factor (SRF) to initiate the transcription of CArG-box-containing genes, such as alpha-smooth muscle actin [PMID: 12393550]. The activity of MRTF-B is tightly regulated by the Rho-actin signaling pathway; when globular actin (G-actin) polymerizes into filamentous actin (F-actin), MRTF-B is released from G-actin and translocates to the nucleus [PMID: 14532133]. This mechanism is a key driver in pathological processes such as the epithelial-mesenchymal transition (EMT) and the activation of myofibroblasts during organ fibrosis in the lungs, kidneys, and heart [PMID: 25100227]. In oncology, MRTF-B is frequently upregulated and contributes to tumor cell migration, invasion, and metastasis across various cancers [PMID: 24631357]. Therapeutic development focuses on small molecule inhibitors, such as CCG-1423 and its analogs, which block its nuclear entry or its interaction with SRF [PMID: 23952213]. Additionally, experimental approaches targeting MRTF-B mRNA via antisense oligonucleotides or siRNA are being explored to treat fibrotic diseases and aggressive malignancies [PMID: 28438784].

Other names

Megakaryoblastic leukemia 2MKL2MRTFBMAL16

Inhibition of MRTF-B nuclear translocation and disruption of the MRTF-B/SRF transcriptional complex [PMID: 23952213]