LAUSR

The NF‐E2 p45‐related factor 2 (NRF2)–Kelch‐like ECH‐associated protein 1 signaling pathway plays an important role in cytoprotection. In acute promyelocytic leukemia, fusion of the promyelocytic leukemia protein (PML) with retinoic acid receptor alpha (RARα) results in an oncogene, PML‐RARα (PR). Although previous studies have shown that both RARα and PML inhibit NRF2 activity, how PR regulates NRF2 has not been reported. Here, we discovered that PR‐S, the short isoform of PR, potentiates NRF2 activity in a tert‐butylhydroquinone (tBHQ) concentration‐dependent manner. Furthermore, PR‐S colocalized with NRF2 in HeLa and HEK293T cells. The association of PR‐S and NRF2 is mediated by the DNA‐binding domains of RARα and the Neh7 domain of NRF2. Our results define a novel function of PR‐S as a NRF2‐transcriptional co‐activator.