VGLL3 (F6X1O) Rabbit Monoclonal Antibody #92094

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 (2-4). VGLL proteins function as YAP/TAZ antagonists by competitively excluding YAP/TAZ from TEAD transcriptional complexes. Transcription cofactor VGLL protein 3 (VGLL3) expression is limited to placenta and adipose tissue, with low or negative expression in other normal tissues (4). Placental trophoblasts express both VGLL1 and VGLL3, and VGLL3 protein can be detected in first-trimester normal plasma as a pregnancy biomarker (4,5). VGLL3 regulates trophoblast differentiation, and aberrant VGLL3-TEAD1 expression causes dysregulation of the trophoblast transcriptome and ultimately preeclampsia (6). In adipose tissue, VGLL3 functions as an inhibitor of adipocyte differentiation by suppressing PPAR gamma expression (7,8). VGLL3 overexpression has been observed in osteosarcoma, gastric cancer, and malignant breast cancer (2,9,10). In multiple tumor models, VGLL3 promotes the expression and activation of Hippo-pathway kinase LATS2, significantly reducing both YAP/TAZ expression and nuclear localization (10). VGLL3 expression can rescue cancer cells from pharmacological YAP/TAZ/TEAD inhibition, bypassing Hippo pathway intervention by directly increasing SOX4/PI3K expression and driving Akt activation (11).

VGLL3 may have a redundant function with VGLL2 in driving myoblast differentiation (12,13). However, VGLL3^-/- mice have no outward skeletal muscle phenotype (12,13). After myocardial infarction or hepatic injury, VGLL3 expression is induced in cardiac and liver myofibroblasts, where it promotes the expression of type I, II, and VI collagens and tissue fibrosis in a TGF-beta-driven pathway (14). Uniquely among the VGLL proteins, VGLL3 can be recruited to DNA double-strand breaks, where it contributes to RAD51-mediated homologous recombination by protecting MDC1 and CtIP from proteasomal degradation (15).