The p53 protein is a sequence-specific DNA-binding factor that regulates inflammatory genes such
as CCL2/MCP-1 that may play a role in various diseases. A recent study has indicated that the knockdown of
human p53 leads to a strong negative regulation of CCL2 induction. We are therefore interested in how p53
regulates CCL2 gene expression. In the following study, our findings indicate that UV-induced p53
accumulation in mouse macrophages significantly decreases LPS-induced CCL2 production, and that p53
binds to CCL2 5’UTR in the region (16-35). We also found that a p53 domain (p53pep170) mimics full length
p53 to down-regulate CCL2 promoter activity. Treatment of p53-deficient mouse primary macrophages with
synthetic p53pep170 was found to decrease LPS-induced production of CCL2 without association with cellular
endogenous p53. CCL2 production induced by lentiCLG in human monocytes or mouse primary macrophages
was blocked in the presence of p53pep170. Overall, these results demonstrate that p53 or its derived peptide
(p53pep170) is an important regulator of CCL2 gene expression via its binding activity, and acts as a novel
model for future studies linking p53 and its short peptide to pave the way to possible pharmaceutical
intervention of CCL2-mediated inflammatory and cancer diseases.
Keywords: p53, CCL2, transcriptional regulation, macrophage, infection, apoptotic signaling pathways, isoforms, tumors, proinflammatory cytokines, mutation, autoimmune disorders, inflammation, genes, chemokines, rheumatoid arthritis.
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