VGLL4 (F5U7N) Rabbit Monoclonal Antibody #60429

TEA domain (TEAD) family proteins function as transcriptional cofactors that interact with nuclear-localized YAP/TAZ to drive expression of cell proliferation and apoptosis genes downstream of Hippo pathway inactivation (1). An additional layer of Hippo pathway control is exerted by the mammalian vestigial-like (VGLL) proteins, a family of transcriptional cofactors that are orthologs of the D. melanogaster protein vestigial (2). VGLL1-4 all contain at least one conserved Tondu motif (TDU) that is crucial for binding TEAD family proteins (2,3). VGLL proteins function as YAP/TAZ antagonists by competitively excluding YAP/TAZ from TEAD transcriptional complexes. Transcription cofactor VGLL protein 4 (VGLL4), which has broad tissue expression and uniquely contains two C-terminal TDU sequences, functions as a tumor suppressor in a variety of contexts by silencing YAP/TAZ signaling; it has been well characterized as a mediator of differentiation in normal tissues, including heart, pancreas, skeletal muscle, and bone (3-7). In colorectal cancer (CRC), VGLL4 expression is negatively correlated with YAP and its target gene CTGF, and VGLL4 overexpression can blunt CRC tumor growth (8). In mutant Merlin meningiomas, high YAP/CTGF expression is observed in benign tumors, while high VGLL4, FAT3, and FAT4 expression suppresses YAP/CTGF activity and expression in high-grade tumors (9). YAP/TEAD inhibitors have emerged as novel reagents for modulating the Hippo-YAP-TEAD pathway, and a subset of small-molecule inhibitors functions as molecular glue enhancers of the TEAD-VGLL4 complex (10).