Transcription Factor NF-?B Regulate The Transcription Of AGGF1

The NF-?B family of transcription factors plays a critical role in regulation the expression of a wide variety of genes, and it also plays an important role in the regulation of lymphocyte activation and proliferation process, particularly in the inflammatory process. The NF-?B family has five members, but only p65, RelB and c-Rel subunit have the transcription activation domain. In a cell in which NF-?B is not active, the members of the NF-?B family are normally kept inactive in the cytoplasm by being bound with the I?B inhibitory proteins. When cells are stimulated, the I?B is degraded, and wiil be dissociated from the inhibitory protein, which allows NF-?B to be activated and translocated to the nucleus to regulate the downstream genes. Q uinacrine(QC) is a type of anti- malaria drugs, but also possess anti- inflammatory and tumor suppressor functions, and is always used as an inhibitor of NF-?B in experimental stud ies. AGGF1 is a newly discovered vascular growth factor, and the recent research indicates that AGGF1 could be an anti- inflammatory factor. AGGF1 has two opposing functions in promoting tumor growth and inhibiting tumor growth, which makes the research of the mechanism of transcriptional regulation of AGGF1 in vivo particularly important. The analysis of the promoter region of AGGF1 by bioinformatics analysis has shown that there are three potential binding sites of NF-?B in the promoter region. The luciferase analysis results show that p65 can bind to the AGGF1 promoter region through two binding sites, and enhance its transcriptional activity. The transcriptional activity of AGGF1 promoter increases nearly 30 times with over-expression of p65, while the activity is reduced significantly, when two binding sites are mutated, by about 61% and 87%, respectively. With the sip65 and QC treatment, the activity of AGGF1 promoter is significantly decreased. The AGGF1 RNA and protein expression analyses show that p65 can increase the expression of AGGF1 RNA and protein. The expression of AGGF1 RNA is increased 1.9 times and the protein expression is also increased under overexpression of p65. With the sip65 and QC treatment, the expression of AGGF1 RNA and the protein is significantly reduced. The experimental datas show that, p65 can regulat the transcription of AGGF1 and promote its protein expression.