title: TP53inp1 Gene Is Implicated in Early Radiation Response in Human Fibroblast Cells.
abstract: Tumor protein 53-induced nuclear protein-1 (TP53inp1) is expressed by activation via p53 and p73. The purpose of our study was to investigate the role of TP53inp1 in response of fibroblasts to ionizing radiation. γ-Ray radiation dose-dependently induces the expression of TP53inp1 in human immortalized fibroblast (F11hT) cells. Stable silencing of TP53inp1 was done via lentiviral transfection of shRNA in F11hT cells. After irradiation the clonogenic survival of TP53inp1 knockdown (F11hT-shTP) cells was compared to cells transfected with non-targeting (NT) shRNA. Radiation-induced senescence was measured by SA-β-Gal staining and autophagy was detected by Acridine Orange dye and microtubule-associated protein-1 light chain 3 (LC3B) immunostaining. The expression of TP53inp1, GDF-15, and CDKN1A and alterations in radiation induced mitochondrial DNA deletions were evaluated by qPCR. TP53inp1 was required for radiation (IR) induced maximal elevation of CDKN1A and GDF-15 expressions. Mitochondrial DNA deletions were increased and autophagy was deregulated following irradiation in the absence of TP53inp1. Finally, we showed that silencing of TP53inp1 enhances the radiation sensitivity of fibroblast cells. These data suggest functional roles for TP53inp1 in radiation-induced autophagy and survival. Taken together, we suppose that silencing of TP53inp1 leads radiation induced autophagy impairment and induces accumulation of damaged mitochondria in primary human fibroblasts.
authors.affiliation: Division of Molecular Radiobiology, National Public Health Center-National Research Directorate for Radiobiology and Radiohygiene, Anna 5, Budapest 1221, Hungary. sandor.nikolett@osski.hu.|Doctoral School of Pathological Sciences, Semmelweis University, Üllői 26, Budapest 1089, Hungary. sandor.nikolett@osski.hu.
authors.forename: Nikolett
authors.initials: N
authors.lastname: Sándor
authors.affiliation: Division of Molecular Radiobiology, National Public Health Center-National Research Directorate for Radiobiology and Radiohygiene, Anna 5, Budapest 1221, Hungary. schilling.toth.boglarka@osski.hu.
authors.forename: Boglárka
authors.initials: B
authors.lastname: Schilling-Tóth
authors.affiliation: Division of Molecular Radiobiology, National Public Health Center-National Research Directorate for Radiobiology and Radiohygiene, Anna 5, Budapest 1221, Hungary. kis.eniko@osski.hu.
authors.forename: Enikő
authors.initials: E
authors.lastname: Kis
authors.affiliation: Department of Genetics, Cell and Immunobiology, Semmelweis University, Nagyvárad tér 4, Budapest 1089, Hungary. fodorlilierika@gmail.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Fodor
authors.affiliation: Department of Genetics, Cell and Immunobiology, Semmelweis University, Nagyvárad tér 4, Budapest 1089, Hungary. fruzsimu@gmail.com.
authors.forename: Fruzsina
authors.initials: F
authors.lastname: Mucsányi
authors.affiliation: Division of Molecular Radiobiology, National Public Health Center-National Research Directorate for Radiobiology and Radiohygiene, Anna 5, Budapest 1221, Hungary. safrany.geza@osski.hu.
authors.forename: Géza
authors.initials: G
authors.lastname: Sáfrány
authors.affiliation: Division of Molecular Radiobiology, National Public Health Center-National Research Directorate for Radiobiology and Radiohygiene, Anna 5, Budapest 1221, Hungary. hegyesi.hargita@osski.hu.|Department of Morphology and Physiology, College of Health Care, Semmelweis University, Vas 17, Budapest 1089, Hungary. hegyesi.hargita@osski.hu.
authors.forename: Hargita
authors.initials: H
authors.lastname: Hegyesi
mesh_terms: D001343:Autophagy; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D016922:Cellular Senescence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D055436:Growth Differentiation Factor 15 / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans
chemical_list: C493956:CDKN1A protein, human; D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004272:DNA, Mitochondrial; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D006360:Heat-Shock Proteins; C429767:TP53INP1 protein, human
keywords: CDKN1A; GDF-15; RNA interference; TP53inp1; autophagy; p53-network; radiosensitivity; senescence