Abstract
p63 is a transcriptional factor belonging to p53 family of genes. Beside the role in cancer, partially shared with p53 and the other member p73, p63 also plays exclusive roles in development and homeostasis of ectodermal/epidermal-related organs. Here we show that p63 transcriptionally controls the expression of the matrix metallopeptidase 13 (MMP13). p63 binds a p53-like responsive element in the human promoter of MMP13, thus promoting the activation of its transcription. The catalytic activity of MMP13 is required in high invasion capacity of metastatic cancer cells, however, although p63 and MMP13 expression correlates in cancer patients, their co-expression does not predict cancer patient survival. Our results demonstrate that p63 directly controls MMP13 expression.
Highlights
ΔNp63 is master regulator of epithelial development and differentiation. p63-/- [4952] and ΔNp63-/- selective null-mice [53] present severe development abnormalities, including limb truncations, craniofacial malformations and the lack of an intact epidermis
They showed that ΔNp63-/- epidermal cells express a subset of markers present in embryonic stem cells and fibroblasts induced to pluripotency using Yamanaka factors [64]. p63 has been proven to be involved in cutaneous wound healing [65], still little is known about p63 targets genes during re-epithelialization
In a gene expression-profiling analysis on TAp63 and ΔNp63 overexpressing cells performed by microarray approaches, we identified important subsets of genes, which potentially might be transcriptionally regulated by p63
Summary
P63 is a p53-related transcriptional factor, which plays roles in development and cancer. Different promoter regions control the expression of two N-terminal isoforms, TAp63 and ΔNp63. The substrate specificity of MMP13 indicated that this protease exhibits high proteolytic activity toward fibrillar type I, II, and III collagens [67] It plays crucial roles in physiological processes such as fetal bone development [68], skeletal development [69, 70], articular cartilage and synovial membrane functionality [71]. P63 can transcriptionally control the expression of MMP13 by binding its promoter gene and promoting its expression This finding indicates a novel target gene of p63 that can help to elucidate p63 role in cancer and in the re-epithelialization process during wound healing
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