ATM-Mediated translocation of RanBPM regulates DNA damage response by stabilizing p21 in non-small cell lung cancer

Tanggang Deng1,2, Lin Xie3,4, Chen Xiaofang3

  • 1Center for Clinical Precision Pharmacy, The First Affiliated Hospital, Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, Guangzhou, Guangdong, China. dengtanggang@163.com.

Abstract

Insights

RanBPM stabilizes p21 protein, a key player in DNA damage response (DDR) in non-small cell lung cancer (NSCLC). This finding reveals RanBPM as a novel regulator critical for DDR in NSCLC progression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cellular Biology

Background:

  • Platinum-based chemotherapy is standard for advanced non-small cell lung cancer (NSCLC).
  • DNA damage response (DDR) involves p53 pathway proteins like p21.
  • RanBPM's role in DDR is known, but its mechanism is unclear.

Purpose of the Study:

  • To elucidate the mechanism of RanBPM in regulating DNA damage response (DDR) in non-small cell lung cancer (NSCLC).
  • To investigate the interaction between RanBPM and p21 in NSCLC.
  • To determine the role of RanBPM in p21 protein stability and DDR.

Main Methods:

  • Immunohistochemical staining of NSCLC tissue microarrays to assess RanBPM expression.
  • In vitro and in vivo models to examine RanBPM's role in NSCLC DDR.
  • Immunoblots and ubiquitylation assays to study RanBPM's regulation of protein stability.

Main Results:

  • Lower levels of p21 and RanBPM in NSCLC tissues, with a positive correlation.
  • RanBPM interacts with p21, recruiting USP11 to deubiquitinate and stabilize p21.
  • RanBPM silencing decreased p21; overexpression increased p21, independent of p53 status.
  • RanBPM regulates DDR in a p21-dependent manner; DNA damage promotes RanBPM nuclear translocation via ATM signaling.

Conclusions:

  • RanBPM is a novel regulator of p21 protein stability.
  • RanBPM plays a critical role in regulating DNA damage response (DDR).

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