Pinning down HER2–ER crosstalk in SMRT regulation

SMRT (silencing mediator for retinoic acid and thyroid hormone receptors) is a transcriptional co-repressor that mediates the repressive function of nuclear hormone receptors such as the estrogen receptor (ER). Decreased SMRT levels correlate with acquired tamoxifen resistance in breast cancer, and SMRT restoration might resensitize breast cancer cells to tamoxifen. A new study demonstrates that SMRT protein stability is regulated by phosphorylation-dependent Pin1-catalyzed prolyl-isomerization. Pin1 functions downstream of HER2, positioning it as an important modulator of the crosstalk between ER and growth factor signaling.