Vestigial-like family member 3 (VGLL3)

Vestigial-like family member 3 (VGLL3) is a transcription cofactor that belongs to the Vestigial family and acts primarily as a partner for TEAD transcription factors, modulating their activity in several tissues[4][7]. VGLL3 is mechanosensitive, with its nuclear localization and function regulated by substrate stiffness[4]. It plays key roles in regulating cell proliferation, differentiation (notably promoting myogenic differentiation and inhibiting adipogenesis), and tissue fibrosis (particularly cardiac and liver fibrosis). In cancer, VGLL3 genomic amplification and overexpression promote tumor cell proliferation and migration, partly by enhancing Hippo pathway signaling to suppress YAP/TAZ activity and by facilitating DNA double-strand repair through proteasomal protection of CtIP[1][3][4][7]. It is highly expressed in certain cancers (e.g., malignant breast tumors, osteosarcoma) and functions as a master regulator in female-biased autoimmunity, as well as in various developmental and stress-response pathways[1][3][5][7].

Other names

Transcription cofactor vestigial-like protein 3Vgl-3VGL3Colon carcinoma related protein

Modulation of TEAD-dependent gene expression; Activation of Hippo signaling pathway via LATS2 and AMOTL2, leading to YAP/TAZ inactivation; Promotion of DNA repair by protecting CtIP from proteasomal degradation