THE ALPHA3 helix of TEAD4 determines the specificity of the identified DNA.

On April 5, the international academic journal Oncogene published online the latest research results of the Research Group DNA-binding mechanism of the Hippo pathway transcription factor TEAD4 of the Institute of Biochemistry and Cell Biology/Molecular Cell Science Innovation Center of the Shanghai Institute of Life Sciences of the Chinese Academy of Sciences.
the study sheds light on the mechanism by which the key transcription factor TEAD4 specifically identifies and binds DNA downstream of the Hippo signaling path.
hippo signaling path is playing a key role in the development of biological individuals, especially in the regulation of tissue size, and plays a very important role in tumor occurrence and immune response.
Zhou Zhaocai research team long-term commitment to tumor occurrence and immune response of molecular cell signaling mechanism research, a series of recent work revealed Hippo, TLR and other signaling pathractic pathractic mechanisms and functions in gastrointestinal malignancies and immune response, found a number of new disease diagnosis and treatment markers and drug targets (Nature Communications 2017; Nature Immunology 2015; EMBO Journal 2015; Cancer Cell 2014; Cell Research 2014).
team previously discovered a new mechanism for hippo-YAP signaling pathraps to regulate the development of stomach cancer, identified the potential application value of VGLL4 as a natural antagonists of YAP for gastric cancer diagnosis and treatment, and developed therapeutic polypeptides (Cancer Cell, 201) 4) A new model of interaction between Hippo and Wnt paths has recently been discovered, and VGLL4 has been revealed to target the interaction of the two nuclei to regulate hippo and Wnt paths to inhibit the function of colon cancer (Nature Communications, 2017).
basis, the new work mainly through structural biology, biochemistry and other technical methods, in-depth analysis of the Hippo path downstream key transcription factor TEAD4 specific identification and DNA mechanism, found that TEAD4 alpha3 helix determines the specificity of dna identification; Mainly composed of two site points, corresponding to the identified DNA of the big ditch and small ditch, for any of the points of mutation will make TEAD4 on the target gene promoter's share of a significant decline, greatly hindering THEP-induced TEAD4 activation and target gene transcription, inhibit the growth of stomach cancer cells.
Zhubing, an assistant researcher, and He Feng, a master's student, are co-authors of the paper.
Jinqiu and Jing Nai-ho, researchers at the Institute of Bioinscing, Biotechnology and Cells, provided strong support and assistance to this work.
This work has been supported by the Strategic Pilot Special (Class B) of the Chinese Academy of Sciences, "Molecular Foundation and Regulation of Cell Destiny Plasticity", the National Natural Science Foundation of China and Shanghai, and the relevant data collection has been supported by the National Protein Science Facility (Shanghai) and the Molecular Biology Platform of Biochemistry and Cell Institute.
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