2012年5月24日,Structure在线发表了新加坡分子与细胞生物学研究所洪万进课题组等的一篇题为Structural and Functional Similarity between the Vgll1-TEAD and the YAP-TEAD Complexes的研究论文,报道了Vgll1-TEAD4复合体的三维晶体,并与YAP/TAZ-TEAD复合体进行比较,发现两者结构与功能的相似性。
通过Vgll1-TEAD与YAP-TEAD复合体比较发现,两者结构高度相似。
进一步研究发现,两者的功能也基本一致。他们都具有上调细胞增殖促进基因( proliferation-promoting gene ) 的表达和促进锚定依赖细胞(anchorage-independent cell)增殖的作用。
鉴于Vgll1与YAP/TAZ结构和功能上的相似性,Vgll1也可能具有促使癌细胞增殖的能力。(生物谷Bioon.com)
doi:10.1016/j.str.2012.04.004
PMC:
PMID:
Structural and Functional Similarity between the Vgll1-TEAD and the YAP-TEAD Complexes
Ajaybabu V. Pobbati, Siew Wee Chan, Ian Lee, Haiwei Song, Wanjin HongSee Affiliations
Hint: Rollover Authors and Affiliations
Cell Biology in Health and Disease Division, Institute of Molecular and Cell Biology, Proteos, Singapore 138673
Structural Biology and Drug Discovery, Institute of Molecular and Cell Biology, Proteos, Singapore 138673
Genome Institute of Singapore, Genome, Singapore 138672
Department of Biochemistry, National University of Singapore, Singapore 117543
Highlights
Vgll1-TEAD complex is structurally similar to the YAP-TEAD complex
Structural similarity is striking as Vgll1 and YAP have a different primary sequence
These complexes upregulate proliferation-promoting genes
They also induce anchorage-independent cell proliferation
Summary
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.