Control of antioxidative response by the tumor suppressor protein PML through regulating Nrf2 activity

Shuang Guo, Xiwen Cheng, Jun Hee Lim, Yu Liu, Hung Ying Kao

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Oxidative stress is a consequence of an imbalance between reactive oxygen species (ROS) production and the ability of the cytoprotective system to detoxify the reactive intermediates. The tumor suppressor promyelocytic leukemia protein (PML) functions as a stress sensor. Loss of PML results in impaired mitochondrial complex II activity, increased ROS, and subsequent activation of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidative pathway. We also demonstrate that sulforaphane (SFN), an antioxidant, regulates Nrf2 activity by controlling abundance and subcellular distribution of PML and that PML is essential for SFN-mediated ROS increase, Nrf2 activation, antiproliferation, antimigration, and antiangiogenesis. Taking the results together, we have uncovered a novel antioxidative mechanism by which PML regulates cellular oxidant homeostasis by controlling complex II integrity and Nrf2 activity and identified PML as an indispensable mediator of SFN activity.

Original languageEnglish
Pages (from-to)2485-2498
Number of pages14
JournalMolecular Biology of the Cell
Volume25
Issue number16
DOIs
Publication statusPublished - 2014

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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