Identification The Interaction Domain And Function Research Betwwen FOXP3 And UXT

CD4+CD25+T Regulatory T cells(Tregs) represent the only currently known population of CD4+T lymphocytes acting as dedicated mediators of dominant tolerance, whose suppressor function is vital for the maintenance of immune homeostasis. Transcriptional factor Foxp3 play the central role in establishing and maintaining the Treg cell transcriptional program. Mice and humans harboring a loss of function mutation in the Foxp3 gene are affected by fatal early onset lymphoproliferative immune-mediated disease affecting a variety of organs and tissues.The mutation of Foxp3 in mice results in lethality about three weeks after birth due to severe dermatitis, multi-organ lymphocyte infiltration and autoimmune hemolytic anemia, and the phenotyp similar to TGF-βand CTLA-4 deficient mice. FOXP3 mutations in the human will lead to immune disorders, endocrine disorders, enteropathy, X chromosome-linked syndrome (IPEX), performance for the full immune disorders, autoimmune endocrine diseases, such as with early onset the I diabetes and thyroiditis. FOXP3 is also widely distributed in many tumor cells, involved in tumorigenesis and immune escape. Thus, FOXP3 play an important role in immune regulatory. Given the central role of Foxp3 in the negative immune regulation,there is little known about how Foxp3 executes this program and how Foxp3 expression is regulated. Taking into account that most of transcriptional function act by protein interactions, screening of interacting proteins of Foxp3 will facilitate an understanding of the regulatory mechanism.In 2008, doctor Changli Jiang screen 9 interaction proteins of Foxp3 by yeast two-hybrid from human leukocyte library and confirmed interaction between Foxp3 and UXT by further co-immunoprecipitation, yeast backcross experiments. To identify the interaction domain and research the biological function of the interaction, the following three aspects have been done.First, in order to clarify the interaction domain,5 Truncated using for yeast two-hybrid were designed and constructed according to the structural characteristics of FOXP3; Then we found that the proline-rich domain in the N terminal of Foxp3 play an important role for the interaction by co-immunoprecipitation and Yeast two-hybrid; In addition, we have done some research in the function of Foxp3 and UXT interaction. Recent studies showed that Foxp3 not only expressed in T lymphocyte, but also in tumor cells which probably engaged in the immune escape of tumor.Our analysis showed that Foxp3 take involved in UXT regulation of transcriptional activity of ER and decrease the transcriptional activity of UXT.In summary, we have determined that the N-terminal proline rich domain of FOXP3 play an important role in the interaction by yeast two-hybrid and immunoprecipitation. And found that FOXP3 can inhibit UXT on ER transcriptional activity. Moreover, these work will lay a basis for the elucidation of Foxp3 action.