Structural and functional similarity between the Vgll1-TEAD and the YAP-TEAD complexes.
The structure of the complex between the transcription cofactor Vgll1 and the transcription factor TEAD4, the mammalian equivalent of the Drosophila Vestigial and Scalloped, respectively, is determined in this study. Remarkably, Vgll1 interacts with TEAD in a manner similar to the transcription coactivators, as well as oncogenes YAP and TAZ, despite having a varied primary sequence. Vgll1-TEAD complex upregulates the expression of IGFBP-5, a proliferation-promoting gene, and facilitates anchorage-independent cell proliferation. The YAP/TAZ-TEAD complex also upregulates several other proliferation-promoting genes and also promotes anchorage-independent cell proliferation. Given its structural and functional similarity to YAP/TAZ, Vgll1 has the potential to promote cancer progression.
Cell Biology in Health and Disease Division, Institute of Molecular and Cell Biology, Proteos, Singapore 138673. ajaybabuvp@imcb.a-star.edu.sg
Ajaybabu V
AV
Pobbati
Siew Wee
SW
Chan
Ian
I
Lee
Haiwei
H
Song
Wanjin
W
Hong
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D049109:Cell Proliferation; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D040681:Structural Homology, Protein; D000091262:TEA Domain Transcription Factors; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D000091102:YAP-Signaling Proteins
D004268:DNA-Binding Proteins; C502521:Dis3 protein, Drosophila; D029721:Drosophila Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D000091262:TEA Domain Transcription Factors; C101204:Tead4 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C400682:VGLL1 protein, human; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila