Chromatin-binding protein that converts stress signals into a program of gene expression that empowers cells with resistance to the stress induced by a change in their microenvironment. Interacts with MSL1 and inhibits its activity on histone H4 'Lys-16' acetylation (H4K16ac). Binds the RELB promoter and activates its transcription, leading to the transactivation of IER3. The NUPR1/RELB/IER3 survival pathway may provide pancreatic ductal adenocarcinoma with remarkable resistance to cell stress, such as starvation or gemcitabine treatment. In breast cancer cells, NUPR1 overexpression leads to the activation of PI3K/AKT signaling pathway, CDKN1A/p21 phosphorylation and relocalization from the nucleus to the cytoplasm, leading to resistance to chemotherapeutic agents, such as doxorubicin.