Parp7 and mono‐adp‐ribosylation negatively regulate estrogen receptor α signaling in human breast cancer cells

Abstract

ADP‐ribosylation is a post‐translational protein modification catalyzed by a family of proteins known as poly‐ADP‐ribose polymerases. PARP7 (TIPARP; ARTD14) is a mono‐ADP‐ribosyl-transferase involved in several cellular processes, including responses to hypoxia, innate immunity and regulation of nuclear receptors. Since previous studies suggested that PARP7 was regulated by 17β‐estradiol, we investigated whether PARP7 regulates estrogen receptor α signaling. We con-firmed the 17β‐estradiol‐dependent increases of PARP7 mRNA and protein levels in MCF‐7 cells, and observed recruitment of estrogen receptor α to the promoter of PARP7. Overexpression of PARP7 decreased ligand‐dependent estrogen receptor α signaling, while treatment of PARP7 knockout MCF‐7 cells with 17β‐estradiol resulted in increased expression of and recruitment to estrogen receptor α target genes, in addition to increased proliferation. Co‐immunoprecipitation as-says revealed that PARP7 mono‐ADP‐ribosylated estrogen receptor α, and mass spectrometry mapped the modified peptides to the receptor’s ligand‐independent transactivation domain. Co-immunoprecipitation with truncated estrogen receptor α variants identified that the hinge region of the receptor is required for PARP7‐dependent mono‐ADP‐ribosylation. These results imply that PARP7‐mediated mono‐ADP‐ribosylation may play an important role in estrogen receptor positive breast cancer.