title: Decrease of mitochondrial p53 during late apoptosis is linked to its dephosphorylation on serine 20.
abstract: Following a genotoxic stress, the tumor suppressor p53 translocates to mitochondria to take part in direct induction of apoptosis, via interaction with BCL-2 family members such as BAK and BAX. We determined the kinetics of the mitochondrial translocation of p53 in HCT-116 and PA-1 cells exposed to different genotoxic stresses (doxorubicin, camptothecin, UVB). This analysis revealed an early escalation in the amount of mitochondrial p53, followed by a peak amount and a decrease of mitochondrial p53 at later time points. We show that the serine 20 phosphorylated form of p53 is present at the mitochondria and that the decrease of p53 mitochondrial level during late apoptosis correlates with a decrease of Ser-20 phosphorylation. Moreover, the S20A p53 mutant translocates well to mitochondria after a genotoxic stress but its mitochondrial localization is very low during late apoptosis when compared to wt p53. The S20A mutant also appears to be compromised for interaction with BAK. We propose here that the level of serine 20 phosphorylation is influential on p53 mitochondrial localization during late apoptosis. Additionally, we report the presence of a new ≃45 kDa caspase-cleaved fragment of p53 in the cytosolic and mitochondrial fractions of apoptotic cells.
authors.affiliation: a Laboratory of Molecular and Cellular Biology; Institute of Life Sciences; Université Catholique de Louvain ; Louvain-la-Neuve , Belgium.|b URPHYM (Unité de Recherche en Physiologie Moléculaire); University of Namur ; Namur , Belgium.
authors.forename: Cédric
authors.initials: C
authors.lastname: Castrogiovanni
authors.affiliation: a Laboratory of Molecular and Cellular Biology; Institute of Life Sciences; Université Catholique de Louvain ; Louvain-la-Neuve , Belgium.
authors.forename: Marie
authors.initials: M
authors.lastname: Vandaudenard
authors.affiliation: c Earth and Life Institute / Biodiversity; Université Catholique de Louvain ; Louvain-la-Neuve , Belgium.
authors.forename: Béranger
authors.initials: B
authors.lastname: Waterschoot
authors.affiliation: b URPHYM (Unité de Recherche en Physiologie Moléculaire); University of Namur ; Namur , Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: De Backer
authors.affiliation: a Laboratory of Molecular and Cellular Biology; Institute of Life Sciences; Université Catholique de Louvain ; Louvain-la-Neuve , Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Dumont
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D002166:Camptothecin / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D045325:HCT116 Cells; D006801:Humans; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D021381:Protein Transport; D059748:Proteolysis; D012694:Serine / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; C494772:BAK1 protein, human; D024101:Mitochondrial Proteins; D010446:Peptide Fragments; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; D012694:Serine; D004317:Doxorubicin; D020169:Caspases; D002166:Camptothecin
keywords: BAK; apoptosis; caspase; mitochondria; p53; phosphorylation; serine 20