Skip to main content
. 2021 Mar 2;7:44. doi: 10.1038/s41420-021-00425-z

Fig. 4. HRD1 modulates NRF2 through ubiquitination degradation.

Fig. 4

A Colocalization of HRD1 and NRF2 in H/R-exposed TCMK-1 cells. Confocal microscopy analysis; Pearson’s correlation coefficient; scale bar = 50 μm; ×600 magnification. **P < 0.01 vs. normal control group (n = 6). B HRD1 and NRF2 coexisted in the precipitated complexes of H/R-exposed TCMK-1 cells. IP immunoprecipitation, IB immunoblot,. C Silencing of HRD1 led to an increase in NRF2 level, while overexpression of HRD1 caused a reduction in NRF2 level. D HRD1 overexpression promoted NRF2 ubiquitylation and degradation, and subsequently reduced NRF2 level in HEK-293T cells. E The QSLVPDI motif on NRF2 constituted an active site for its interaction with HRD1. F The deletion of QSLVPDI amino acids sequence (Δ125–131) remarkably decrease ubiquitylation of NRF2 mediated by HRD1. G Graphical illustration of the working mechanism: XBP1/HRD1 is involved in IR-induced AKI through the regulation of NRF2/HO-1-mediated ROS signaling.