YAP1-MAML2 gene fusion protein domains. (A) Structural domains of the YAP1 gene include the TEAD1-interaction domain (amino acids 50–171) and two WW1 protein interaction domains with unknown function. MAML2 contains a Notch-interaction domain (somewhere within amino acids 1–172), which is responsible for MAML2 transactivation function in the presence of Notch signaling. Transactivation domain of MAML2 is located somewhere within amino acids 172–1156. The two genes are fused at the amino acid 191 of YAP1 gene and 172 of MAML2 gene. The resulting gene (B) contains the TEAD1-interaction domain and a truncated WW1 domain from YAP1 and the transactivation domain from MAML2. (C) Under the proposed model, the fusion protein is recruited via TEAD1 binding to target genes of TEAD1, many of which are important in embryonic stem cells (ESCs). Because the MAML2 Notch interaction domain is absent, transactivation of ESC target genes may occur constitutively, possibly leading to dedifferentiation or proliferation.
