Mastermind-like transcriptional coactivator 3 (MAML3)

Mastermind-like transcriptional coactivator 3 (MAML3) is a nuclear protein that acts as a versatile transcriptional coactivator. It is a member of the mastermind-like family, functioning primarily in the nucleus to integrate Notch signaling with other pathways, including the WNT/β-catenin and IGF1R/AKT cascades, thereby modulating cell fate, differentiation, and proliferation. MAML3’s canonical role involves binding to intracellular Notch domains and promoting transcription by RNA polymerase II; however, recurrent MAML3 gene fusions (e.g., UBTF–MAML3) have been found in aggressive cancers such as pheochromocytomas, paragangliomas, sarcomas, and others, where they drive aberrant gene expression programs that contribute to tumorigenicity, invasion, and therapy resistance. Aberrant expression or gene fusion of MAML3 is associated with poor prognosis and increased metastatic potential in several cancer types. In non-cancer contexts, MAML3 has associations with other biological processes including angiogenesis and bronchial hyperresponsiveness in asthma.

Other names

Mastermind-like protein 3KIAA1816Mam-3MAM2CAGH3GDNTNRC3ERDA3CAG repeat containing (glia-derived nexin I alpha), expanded repeat domainCAG/CTG 3polyglutamine richtrinucleotide repeat containing 3MAML3