Mastermind like transcriptional coactivator 2 (MAML2)

Mastermind like transcriptional coactivator 2 (MAML2) is a nuclear protein that acts as a transcriptional coactivator in the Notch signaling pathway, which is essential for cell-fate determination, cell proliferation, and differentiation. MAML2 interacts with the intracellular domains of Notch receptors (ICN1–4) and the CSL (CBF1, Suppressor of Hairless, Lag-1) transcription factors to form a complex that activates transcription of Notch target genes. MAML2 contains a conserved domain that binds Notch and a C-terminal transcriptional activation domain. It is widely expressed and has a significant role in various cancers, especially when chromosomal translocations generate fusion proteins (e.g., CRTC1-MAML2) that drive tumorigenesis, notably in mucoepidermoid carcinoma. There are no drugs clinically approved to target MAML2 specifically, but it is considered a potential target due to its centrality in Notch-mediated transcription and cancer development. Its normal activity is vital for development and tissue maintenance, so drugging it carries significant safety concerns[2][3][4].

Other names

MAML2Mastermind-like protein 2

Drugs targeting MAML2 would be expected to inhibit or disrupt Notch transcriptional coactivation, thereby modulating Notch-dependent gene expression and associated cell fate/proliferation signals[3][4].