Nuclear protein 1 (Nupr1/com1/p8) transcriptionally regulates p21 in breast cancer cells

2102 Nuclear protein 1 (Nupr1), also known as p8 or candidate of metastasis-1, is often up-regulated in both primary tumors and metastases, including breast and pancreatic cancer as well as thyroid neoplasms. Nupr1 is upregulated in response to stress, including serum-deprivation, oxidative stress, staurosporine and doxorubicin. This study investigates the potential role of Nupr1 in cell-cycle control in breast cancer via transcriptional regulation of a cell cycle arrest gene, p21CIP1. Luciferase assays using the p21 promoter showed that Nupr1 is capable of stimulating expression of p21, and that this stimulation is largely abrogated in the presence of a p53 dominant-negative mutant as well as the oncogenic p300-binding protein, E1A. p300 and p53 interact and bind to the promoter of p21 to activate transcription. p300 has been identified as an interactor of Nupr1, and hence we checked if Nupr1 is also able to interact with p53. Our immunoprecipitation experiments indicate an interaction between p53 and Nupr1 in a breast tumor cell line as well as in human embryonic kidney cells. Nupr1 is capable of binding DNA, but appears to require a partner to convey specificity; therefore, it is logical to speculate that Nupr1 associates with p53 and p300, and that this complex binds the p21 promoter to stimulate transcription. The results thus disclose a putative important new role for Nupr1 in the regulation of gene transcription.