Investigation The Function Of TEAD4 And T-TEAD4 In Colorectal Cancer

Hippo signaling pathway is mainly involved in mammalian cell development,organ size control,the main feature of the pathway is through the signal cascade pathway regulation YAP and TAZ phosphorylation,and thus control the process of YAP/TAZ protein enter into the nucleus,and interacted with transcriptional factors like TEADs.TEADs protein family and co-transcription factor YAP and TAZ are exacative down stream components of Hippo signal pathway.TEAD protein family is a class of transcription factors,which a total ofhas four members.TEAD protein family and transcription factor YAP protein,TAZ protein and so on are Hippo signal pathway downstream part.Hippo signaling pathway is mainly involved in mammalian development,organ size control,the main feature of the pathway is through the signal cascade pathway regulation YAP protein,TAZ protein phosphorylation,and thus control the YAP protein,TAZ protein into the nucleus process.TEADThis protein has two main functional domains,namely DNA binding region domain and YAP//TAZ binding regiondomain,which itself does not have possess transcriptional activation domain,while.Tthe YAP protein,/TAZ protein has transcriptional activation function but can not bind to DNA,only TEADs protein and YAP/or TAZ binding to form a complete complexe possess both DNA binding and transcriptional activation function of the complex can play a role in transcriptional activation.The genes regulated by it TAEDs/YAP complex are some proto-oncogenes:s,like CTGF,Cyr61,Myc,Gli2 and so onetc.Studies shown that TEADs family members plays an important role in the development of various tumorscancers,such as ovarian cancer,breast cancer,prostate cancer and so on,however,.T the detailed mechanism is through which the activation of some proto-oncogene transcription,and these genes mainlyand affect cancer cell proliferation,migration,EMT and other processes has not being well explored.And therefore,in current study,we aimed at explore the role of TEAD4 in cancer,especially in colon cancer development and underline molecular mechnisms.I am concerned about the TEAD4 protein is a member of the TEAD protein family.The main conclusions of thefrom our current study are as follows:11,).compared to non-tumor tissues,we detected TEAD4 is highly expressed protein in human colon cancer tissue expression levels were significantly increased.;2).,we also detected found a truncated form of TEAD4 protein,nominated to t-TEAD4 protein.is highly expressed in In ccolorectal cancer cases,t-TEAD4 protein expression levels were significantly increased.tissues compared to non-tumor tissues;3,3).futhermore,we identified the sequence of t-TEAD4 protein.Compared to the full-length TEAD4 protein,t-TEAD4 lacked the N-terminal DNA-binding domain,as well as the nuclear localization signal.but possessed the C-terminal YAP/TAZ binding domain.In the study of t-TEAD4 protein function,we found that it promoted the function of cell proliferation and significantly related with increased the level of cyclinD protein.In the aspect of t-TEAD4 protein production,it was confirmed that the production of t-TEAD4 was a selective regulatory mechanism for the alternative translation initiation site.Future study of this project will be The subject continues to be studied and is currently focused on following two aspects.The first aspect is to study the mechanism of t-TEAD4 to promote cell proliferation and up-regulation of Cyclin D1 protein expression.Since the current study of TEAD4 is focused on the Hippo pathway and the transcription factor function of TEAD4,t-TEAD4 plays a role in promoting cell proliferation and can not be explained by studies of existing Hippo pathways and TEAD4 transcription factors.so it may be through novel Hippo pathway independent manchnism.The second aspect is to the study of the regulatory mechanisms for regulating the initiation ofalternative translation initiation sites through which generated by t-TEAD4,since our current results confirm that the TEOP4 TEAD4 protein truncation is associated with the AUG site on the mRNA level,and that the t-TEAD4 protein is more likely to related with Tthe ribosomes are produced reconized alternative at these AUG sitesstart codon.But how does the ribosome perform the alternative translational site selection,the related cis-acting element,what is the trans-acting factor,and the regulatary which factors regulate,that are invovled in these process,which we need to be further elucidated.