MAO-A

MAML2 (Mastermind-like 2) is a gene that encodes a protein involved in transcriptional coactivation in humans. It is a member of the Mastermind-like family of proteins, which play a crucial role in the Notch signaling pathway, a pathway that is essential for cell differentiation, proliferation, and apoptosis.

Structure

The MAML2 gene is located on chromosome 11q21. The protein encoded by MAML2 contains several domains that facilitate its interaction with other proteins, including the Notch intracellular domain (NICD) and other transcriptional coactivators. The structure of MAML2 allows it to function as a scaffold protein, bringing together various components necessary for transcriptional activation.

Function

MAML2 acts as a transcriptional coactivator in the Notch signaling pathway. Upon activation of the Notch receptor, the NICD is released and translocates to the nucleus, where it interacts with MAML2. MAML2 then recruits additional coactivators and the transcription factor CSL (CBF1/Su(H)/LAG-1) to form a transcriptional activation complex. This complex initiates the transcription of target genes that are involved in cell fate determination, proliferation, and apoptosis.

Clinical Significance

MAML2 is implicated in several human diseases, particularly in certain types of cancer. A well-known chromosomal translocation involving MAML2 is the t(11;19)(q21;p13) translocation, which results in the fusion of the MAML2 gene with the CRTC1 (CREB-regulated transcription coactivator 1) gene. This fusion gene is commonly found in mucoepidermoid carcinoma, a type of salivary gland cancer. The MAML2-CRTC1 fusion protein acts as an oncogene, promoting tumorigenesis by aberrantly activating transcriptional programs.

Research and Therapeutic Implications

Understanding the role of MAML2 in the Notch signaling pathway and its involvement in cancer has significant therapeutic implications. Targeting the MAML2-CRTC1 fusion protein or the Notch signaling pathway could provide novel treatment strategies for cancers associated with MAML2 abnormalities. Research is ongoing to develop inhibitors that specifically disrupt the interaction between MAML2 and its partners in the transcriptional activation complex.

Also see

• Notch signaling pathway
• Transcriptional coactivator
• Mucoepidermoid carcinoma
• Chromosomal translocation
• Oncogene