WITHDRAWN: Caenorhabditis elegans nuclear hormone receptor NHR-14, cooperates with p53/cep-1 to regulate DNA damage-induced apoptosis

Abstract

Nuclear hormone receptor is involved in transcription regulation and many important cellular processes including development and metabolism. However, the role of nuclear hormone receptor in DNA damage-induced apoptosis remains elusive. Here we reported that RNAi of nhr-14, which was thought to be an estrogenic hormone receptor in Caenorhabditis elegans, inhibited DNA damage-induced apoptosis in prmt-5(gk357), a C. elegans homolog of mammalian type II arginine methyltransferase PRMT5, after ionizing radiation. Deletion of nhr-14 led to decreased DNA damageinduced germline apoptosis, but not in the physiological programmed cell death. We also demonstrate that nhr-14 is not a checkpoint gene and functions downstream of the checkpoint pathway. Moreover, we show that nhr-14 regulates egl-1 and ced-13 transcription upon DNA damage. In addition, we provided evidence that NHR-14 forms a complex with CEP-1/p53 and may function as a cofactor of CEP-1/p53. These findings indicate that NHR-14 might cooperate with CEP-1/p53 to regulate DNA damage-induced apoptosis, which reveals a novel role for nuclear hormone receptor in apoptosis.