ATM-Mediated Translocation of RanBPM Regulates DNA Damage Response by Stabilizing p21 in Non-Small Cell Lung Cancer Cells

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-induced deaths around the world, and platinum-based chemotherapy remains a standard-of-care for most patients with advanced NSCLC. DNA damage response (DDR) induced by platinum or Etoposide activated a panel of cell cycle-regulatory proteins including p21 through p53 pathway. In this present study, we found that the level of p21 or RanBPM is lower in NSCLC than non-malignant tissues and has a highly positive correlation, which is negatively correlated with the survival of patients. We further revealed that RanBPM protein physically interacts with p21, RanBPM deubiquitinates p21 by recruiting a deubiquitinase USP11 to maintain protein stability of p21. Furthermore, RanBPM regulates DNA damage response (DDR) in a p21-dependent manner, and DNA damage promotes the translocation of RanBPM into the nucleus and regulates p21 protein stability through ATM-mediated pathways. We for the first time revealed a novel mechanism of p21 protein stability regulated by RanBPM, and the novel roles of RanBPM in the regulation of DDR.

Exploring the mechanism of 6-Methoxydihydrosanguinarine in the treatment of lung adenocarcinoma based on network pharmacology, molecular docking and experimental investigation

“…Cell culture A549 cells were purchased from American Type Culture Collection (ATCC, Manassas, VA) and were cultured in RPMI 1640 medium (CT1875500BT, Gibco, Thermo-Fisher Scientific, USA) supplemented with 10% fetal bovine serum (164210-50, FBS, Procell, Wuhan, Hubei, China) plus penicillin G (15140-122, Gibco, Thermo-Fisher Scientific, USA, 100 U/mL) and streptomycin (15140-122, Gibco, ThermoFisher Scientific, USA,100 U/ mL) at 37 °C under 5% CO 2 [26].…”