title: TAp73 upregulates IL-1β 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-1β (IL-1β) has a crucial role in mediating the inflammatory response. Because of its high potency to induce inflammation, the activation and secretion of IL-1β 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-1β. 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-1β regulation and therefore in the control of the inflammatory response. Our results show that TAp73β upregulates pro-IL-1β mRNA and processed IL-1β protein. In addition, analysis of breast and lung cancer patient cohorts demonstrated that interaction between p73 and IL-1β predicts a negative survival outcome in these human cancers.
authors.affiliation: MRC Toxicology Unit, Hodgkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, United Kingdom.
authors.forename: Polina
authors.initials: P
authors.lastname: Vikhreva
authors.affiliation: MRC Toxicology Unit, Hodgkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, United Kingdom.
authors.forename: Varvara
authors.initials: V
authors.lastname: Petrova
authors.affiliation: MRC Toxicology Unit, Hodgkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, United Kingdom; Erciyes University, Faculty of Science, Department of Biology, 38039 Kayseri, Turkey.
authors.forename: Tarik
authors.initials: T
authors.lastname: Gokbulut
authors.affiliation: Department of Experimental Medicine and Surgery, IDI-IRCCS, University of Rome Tor Vergata, Rome 00133, Italy.
authors.forename: Ilias
authors.initials: I
authors.lastname: Pestlikis
authors.affiliation: MRC Toxicology Unit, Hodgkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, United Kingdom.
authors.forename: Mara
authors.initials: M
authors.lastname: Mancini
authors.affiliation: Department of System Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Di Daniele
authors.affiliation: MRC Toxicology Unit, Hodgkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, United Kingdom.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Knight
authors.affiliation: MRC Toxicology Unit, Hodgkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, United Kingdom; Department of Experimental Medicine and Surgery, IDI-IRCCS, University of Rome Tor Vergata, Rome 00133, Italy.
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
authors.affiliation: MRC Toxicology Unit, Hodgkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, United Kingdom. Electronic address: ia119@le.ac.uk.
authors.forename: Ivano
authors.initials: I
authors.lastname: Amelio
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D000072160:Tumor Protein p73 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C508585:IL1B protein, human; D058847:Inflammasomes; D053583:Interleukin-1beta; D020033:Protein Isoforms; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D020170:Caspase 1
keywords: Cytokines; Immunotherapy; Inflammation; Interleukin; p53 family