Truncated PPM1D impairs stem cell response to genotoxic stress and promotes growth of APC-deficient tumors in the mouse colon

• Published in: Cell death & disease Vol. 10; no. 11; pp. 818 - 15
• Main Authors: Burocziova, Monika, Burdova, Kamila, Martinikova, Andra S., Kasparek, Petr, Kleiblova, Petra, Danielsen, Stine A., Borecka, Marianna, Jenikova, Gabriela, Janečková, Lucie, Pavel, Jozef, Zemankova, Petra, Schneiderova, Michaela, Schwarzova, Lucie, Ticha, Ivana, Sun, Xiao-Feng, Jiraskova, Katerina, Liska, Vaclav, Vodickova, Ludmila, Vodicka, Pavel, Sedlacek, Radislav, Kleibl, Zdenek, Lothe, Ragnhild A., Korinek, Vladimír, Macurek, Libor
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.10.2019; Springer Nature B.V
• Subjects: 13; 13/1; 13/100; 13/106; 13/31; 13/51; 38/23; 5-Fluorouracil; 631/67/70; 631/80/641/2187; 64; 64/60; 82/29; Adenomatous polyposis coli; Adenomatous Polyposis Coli Protein - genetics; Animals; Antibodies; Biochemistry; Biomedical and Life Sciences; Carcinogenesis - drug effects; Cell activation; Cell Biology; Cell Culture; Cell cycle; Cell Cycle Checkpoints - genetics; Cell proliferation; Cell Proliferation - drug effects; Chemotherapy; Chromatin; Chromatin - drug effects; Colonic Neoplasms - drug therapy; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Colorectal cancer; Colorectal carcinoma; Deoxyribonucleic acid; DNA; DNA damage; DNA Damage - drug effects; DNA repair; DNA Repair - drug effects; Exons - genetics; Fluorouracil - pharmacology; Gene Expression Regulation, Neoplastic - drug effects; Genotoxicity; Humans; Immunology; Life Sciences; Magnesium; Mice; Mutation; Mutation - genetics; Organoids; p53 Protein; Protein phosphatase; Protein Phosphatase 2C - genetics; Stem cell transplantation; Stem cells; Tumor suppressor genes; Tumor Suppressor Protein p53 - genetics; Tumorigenesis

Protein phosphatase magnesium-dependent 1 delta (PPM1D) terminates cell response to genotoxic stress by negatively regulating the tumor suppressor p53 and other targets at chromatin. Mutations in the exon 6 of the PPM1D result in production of a highly stable, C-terminally truncated PPM1D. These gai...