Mastermind-like protein 1 (MAML1) (MAML1)

Mastermind-like protein 1 (MAML1) is a transcriptional coactivator that plays an indispensable role in the Notch signaling pathway, a conserved mechanism for cell-fate determination and tissue homeostasis [UniProt: Q92585]. MAML1 acts as a scaffold, forming a ternary complex with the Notch intracellular domain (NICD) and the DNA-binding protein CSL (CBF1/RBPJ) to recruit additional coactivators like p300/CBP, thereby driving the expression of downstream targets such as HES1 and MYC [PubMed: 11051546]. In many cancers, including T-cell acute lymphoblastic leukemia (T-ALL) and various solid tumors, MAML1 is frequently overexpressed or involved in oncogenic Notch signaling, making it a high-priority therapeutic target [PubMed: 24501218]. Targeting MAML1 mRNA or its protein product offers a strategy to inhibit Notch signaling at the nuclear level, potentially avoiding some of the systemic toxicities associated with upstream inhibitors like gamma-secretase inhibitors (GSIs) [PubMed: 19890330]. Experimental approaches include the use of stapled peptides (e.g., SAHM1) to disrupt the protein-protein interface and RNA-based therapies to reduce MAML1 expression [Nature: 462(7270)]. Clinical development of inhibitors targeting the Notch transcription complex, such as CB-103, aims to provide more selective therapeutic options for patients with Notch-dependent malignancies [PubMed: 32571891].

Other names

Mastermind-like 1Mam-1MAML-1Mam1

Inhibition of the assembly of the Notch transcriptional activation complex by preventing the recruitment of MAML1 to the NICD/CSL complex [PubMed: 19890330].