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bioRxiv · 10.1101/2022.12.20.520942

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

deng, t.·xie, l.·xiao, y.·zhang, z.·peng, y.·yin, l.·fu, y.·li, x.
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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.

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deng, t., xie, l., xiao, y., zhang, z., peng, y., yin, l., fu, y., li, x.. 2022-12-20. ATM-Mediated Translocation of RanBPM Regulates DNA Damage Response by Stabilizing p21 in Non-Small Cell Lung Cancer Cells. https://doi.org/10.1101/2022.12.20.520942

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