Sestrin 2 Regulates PDGF Receptor beta (PDGFR{beta}) Expression by Modulating Proteasomal and Nrf2 Transcription Factor Functions [Signal Transduction]

February 25th, 2015 by Tomasovic, A., Kurrle, N., Sueruen, D., Heidler, J., Husnjak, K., Poser, I., Schnuetgen, F., Scheibe, S., Seimetz, M., Jaksch, P., Hyman, A., Weissmann, N., von Melchner, H.

We recently identified the antioxidant protein Sestrin 2 (Sesn2) as a suppressor of platelet derived growth factor receptor beta (PDGFRβ) signaling and PDGFRβ signaling as an inducer of lung regeneration and injury repair. Here, we identified Sesn2 and the antioxidant gene inducer nuclear factor erythroid 2-related factor 2 (Nrf2) as positive regulators of proteasomal function. Inactivation of Sesn2 or Nrf2 induced reactive oxygen species (ROS)-mediated proteasomal inhibition and Pdgfrβ accumulation. Using bacterial artificial chromosome (BAC) transgenic HeLa- and mouse embryonic stem cells stably expressing EGFP-tagged SESN2 at nearly endogenous levels, we also showed that SESN2 physically interacts with 2-Cys peroxiredoxins and NRF2 albeit under different reductive conditions. Overall, we characterized a novel, redox sensitive SESN2/PDGFRβ suppressor pathway that negatively interferes with lung regeneration and is upregulated in the emphysematous lungs of patients with chronic obstructive pulmonary disease (COPD).
  • Posted in Journal of Biological Chemistry, Publications
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