Identification of a Novel Transcriptional Regulatory Element Common to the p53 and Interferon Regulatory Factor 1 Genes

Abstract

The promoter regions of both the interferon regulatory factor (IRF1) and p53 antioncogenes contain a previously unidentified sequence denoted IRF1 p53 common sequence (IPCS), which markedly increases the transcriptional activity of a reporter gene placed under the control of an heterologous promoter in transfected U937 cells. In contrast, transfection of U937 cells with reporter vectors containing p53 and IRF1 promoters with mutated IPCS sites resulted in a 4-fold reduction in the constitutive expression of those two genes. The transcriptional activity of IPCS is strictly correlated with the binding of a novel nuclear factor, IPCS-binding factor (IPCS-BF). IPCS-BF, which is composed of a single polypeptide of 26 kDa, is present constitutively in nuclear extracts of both U937 cells and peripheral blood mononuclear cells from healthy donors. The finding that the pattern of binding of IPCS-BF to the IPCS is unlike that of any known transcription factor and that the IPCS sequence does not exhibit any significant homology with any known binding site present in the data base, strongly suggest that IPCS-BF is a novel transcription factor which, by virtue of this ability to regulate the expression of the p53 and IRF1 genes, could play a central role in the control of cell proliferation and/or apoptosis.

GW body disassembly triggered by siRNAs independently of their silencing activity

“…IFN dosage was performed as previously described (22). Each sample was tested in duplicate and the dosage was repeated twice.…”

MyD genes in negative growth control

“…The transcriptional activity of IPCS was shown to be strictly correlated with the binding of an IPCSbinding factor (IPCS-BF), thereby revealing that the expression of these two growth suppressive genes is under common regulation (Lallemand et al, 1997).…”

Myeloid Differentiation (MyD)/Growth Arrest DNA Damage (GADD) genes in tumor suppression, immunity and inflammation

“…Transcriptional activation of IPCS is strictly dependent on the binding of an IPCS-binding factor (IPCS-BF), indicating that expression of these two growth suppressive genes is also under common regulation. 29 Taken together, what has been discussed above suggests that IRF-1 functions as a tumor suppressor gene whose loss of function contributes to oncogenesis. Consistent with this notion, Harada et al 30 have shown that balanced expression of IRF-1 and IRF-2 is critical for normal cell growth.…”