Authors
Ajaybabu V. Pobbati¹, Siew Wee Chan¹, Ian Lee², Haiwei Song¹ and Wanjin Hong^1,3.

1 - Cell Biology in Health and Disease Division, Institute of Molecular and Cell Biology, Proteos,        Singapore 138673
2 -   Genome Institute of Singapore, Genome, Singapore 138672
3 -   Department of Biochemistry, National University of Singapore, Singapore 117543

Published on-line in Structure on 24 May, 2012

Abstract

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. YAP/TAZ-TEAD complex also upregulate 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.

Figure Legend:
(A) Ribbon diagram representation of the Vgll1-TEAD4 structure. The interaction between these two proteins is divided into two interfaces. TEAD4 is colored red, and Vgll1 is colored green. (B) Superposition of the Vgll1-TEAD4 complex with that of the YAP-TEAD1 (Protein Data Bank 3KYS) complex. YAP is colored orange. The structure of the TEAD4 and TEAD1 in the complex is very similar, and therefore TEAD1 is omitted for clarity. The additional YAP-TEAD interface is labeled as Interface 3. (C) Interfaces 1 and 2 residues of Vgll1 and YAP are aligned. The VxxHF and the LxxLF motif are shown in red.

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