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Research Of Human Cancer Associated Gene FoxP4, Construction, Function And Regulation

Posted on:2007-12-21Degree:MasterType:Thesis
Country:ChinaCandidate:W HuangFull Text:PDF
GTID:2120360182488141Subject:Developmental Biology
Abstract/Summary:PDF Full Text Request
Cancer is the most dangerous killer in all the diseases, and lung carcinoma is the most one in all the cancer. So far, the cancerogenic mechanism of lung cancer is not well elucidated. Some growth factors and growth factor receptors have been identified to participate in cancerogenic processes, but the downstream pathways regulated by those growth factor receptors are uncleared. Clarif ing these pathways and genes are essential to understand the cancerogenic process and design medicines.forkhead box P4 (FoxP4) is one of the candidate genes that the author of this article obtained from the scanning for genes related to heart development with bioinformatics methods. This protein contains a consensus domain of CCHC Zinc finger in N-terminal ( 307aa-332aa ) , a Fork Head(465aa-547aa) domain in C-terminal, and a motif, Coiled Coil, between 343aa to 366aa . In many mammalians, such as mouse, rat, and so on, we discovered the homologues of FoxP4 and they present highly consensus during evolution, which suggests the potential importance of this subfamily. Expression assays present that FoxP4 is expressed with different pattern at fetal of 80 days and strongly expressed in brain, stomach, kidney and lung. The results of transcripteion activity assays show that overexpression of FoxP4 in COS7 cells can remarkably activate the transcriptional activity of SRE, which are downstream effectors of MAPK pathway. Furthermore, overexpression of FoxP4 can slightly promote the growth of Hela cell. In conclusion, we suggest that FoxP4 probably take part in regulation of cell life progress through acting a role in MAPK pathway.Otherwise, Cat D and rcap, two candidates for interacted with FoxP4, were obtained by screening in Yeast two-hybrid system. Interestingly, Cat D is a potent endoprotease and several studies have linked it to apoptosis. For example, it was shown that Cat D is involved in the signal transduction of Fas-mediated cell death. In addition, Cat D plays a role in p53-mediated cell death and triggers the release of cytochrome c from the mitochondria. Therefore we presume that FoxP4 is involved in apoptosis. In addition a Z disc Tcap , a Titin interacting protein, is a key component of the in vivo cardiomyocyte stretch sensor machinery, and it provide a research clue for us to investigate the function of FoxP4 in other way.
Keywords/Search Tags:FoxP4, MAPK, transcriptional activity
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