Enhanced DNA-repair capacity and resistance to chemically induced carcinogenesis upon deletion of the phosphatase regulator NIPP1

Autor: Louise Van Wijk, Shannah Boens, Aleyde Van Eynde, Mathieu Bollen, Iris Verbinnen, Mónica Ferreira, Kathelijne Szekér
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Oncogenesis, Vol 9, Iss 3, Pp 1-8 (2020)
Oncogenesis
ISSN: 2157-9024
DOI: 10.1038/s41389-020-0214-3
Popis: Nuclear Inhibitor of PP1 (NIPP1) is a conserved regulatory subunit of protein phosphatase PP1. The selective deletion of NIPP1 in mouse liver parenchymal cells or skin epidermal cells culminates in a late-onset hyperproliferation of a subset of resident progenitor cells. Although a hyperplastic phenotype is usually tumor promoting, we show here that the absence of NIPP1 conferred a strong resistance to chemically induced hepatocellular or skin carcinoma. The ablation of NIPP1 did not affect the metabolism of the administered mutagens (diethylnitrosamine or 7,12-dimethylbenz[a]anthracene), but reduced the conversion of mutagen-induced covalent DNA modifications into cancer-initiating mutations. This reduced sensitivity to mutagens correlated with an enhanced DNA-damage response and an augmented expression of rate-limiting DNA-repair proteins (MGMT in liver, XPD and XPG in skin), hinting at an increased DNA-repair capacity. Our data identify NIPP1 as a repressor of DNA repair and as a promising target for novel cancer prevention and treatment therapies. ispartof: ONCOGENESIS vol:9 issue:3 ispartof: location:United States status: published
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje