Vestigial like family member 4 (VGLL4)

Vestigial like family member 4 (VGLL4) is a nuclear transcriptional cofactor that belongs to the vestigial-like (VGLL) family (VGLL1-4), characterized by its two Tondu (TDU) domains.[1][3][4] VGLL4 does not bind DNA directly but regulates transcription by interacting with TEA domain (TEAD) transcription factors, chiefly via its TDU domains, and competes with Yes-associated protein (YAP) for TEAD binding.[1][2][3][4] This competition antagonizes YAP-driven gene expression, thereby regulating processes such as cellular proliferation, differentiation, and tumor suppression.[1][3][4] VGLL4 acts as a tumor suppressor, with lower expression indicating poorer prognosis in several cancers.[3][4] In muscle, VGLL4 orchestrates a balance between stem cell proliferation and myogenic differentiation through stage-specific TEAD4 interactions, also serving as a co-activator with MyoD at later stages.[1] Small molecules such as Compound 2 and VT-103 can induce a cofactor switch, favoring VGLL4-TEAD over YAP-TEAD complexes, representing a novel therapeutic strategy in oncology and potentially other VGLL4-associated diseases.[2][3][4]

Other names

Transcription cofactor vestigial-like protein 4KIAA0121Vgl-4VGL-4Vestigial-like 4vestigial like 4

Inhibition of YAP–TEAD activity via cofactor switching (VGLL4 competes with YAP for TEAD DNA binding, suppressing YAP-driven transcription)