Myb-related protein A (MYBL1)

Myb-related protein A (MYBL1) is a member of the MYB family of transcription factors, which regulate gene expression by binding to specific DNA sequences. MYBL1 acts as a potent activator of transcription and shares structural features with MYB and MYBL2, including an N-terminal DNA-binding domain and a unique negative regulatory region at the C-terminus. Physiologically, MYBL1 is essential for male meiosis, proper breast development, and regulation of differentiation and cell proliferation. Pathologically, its genomic alterations—such as overexpression, truncation, and gene fusions—are found in various cancers (e.g., hepatocellular carcinoma, gliomas, triple-negative breast cancer, adenoid cystic carcinoma). These alterations drive tumor growth, metastatic capacity, and resistance to therapies (notably via regulation of oncogenes like MYC, TWIST1, and angiogenic genes ANGPT1/2). While no direct MYBL1-targeted therapies exist, its genetic and expression status is increasingly explored as a prognostic cancer biomarker and a potential targetable vulnerability.

Other names

MYB proto-oncogene like 1MYBL1Myb-related protein AAMYBA-MybA-mybmyb-like protein 1v-myb avian myeloblastosis viral oncogene homolog-like 1

Hypothetical mechanisms (if drugs were developed): transcriptional inhibition, blockade of DNA-binding domain, or disruption of oncogenic fusions. Sorafenib resistance mechanism may involve MYBL1-induced angiogenic pathways.