TAp73 upregulates IL-1? in cancer cells: Potential biomarker in lung and breast cancer?

ABSTRACT: p73 is a transcription factor belonging to the p53 tumour suppressor family. p73^-/- mice exhibit a range of phenotypes including neurological, reproductive and inflammatory defects. Although the role of p73 in the control of genomic stability explains part of these phenotypes, a clear mechanism of how p73 participates in the inflammatory response is still elusive. Interleukin-1? (IL-1?) has a crucial role in mediating the inflammatory response. Because of its high potency to induce inflammation, the activation and secretion of IL-1? is tightly regulated by large protein complexes, named inflammasomes. Inflammasomes regulate activation of proinflammatory caspase-1, which in turn proteolytically processes its substrates, including pro-IL-1?. Caspase-1 gene transcription is strongly activated by p53 protein family members including p73. Here, we have addressed whether p73 might be directly involved in IL-1? regulation and therefore in the control of the inflammatory response. Our results show that TAp73? upregulates pro-IL-1? mRNA and processed IL-1? protein. In addition, analysis of breast and lung cancer patient cohorts demonstrated that interaction between p73 and IL-1? predicts a negative survival outcome in these human cancers.

SUBMITTER: Vikhreva P 

PROVIDER: S-EPMC5243147 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature