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. Author manuscript; available in PMC: 2021 Dec 1.
Published in final edited form as: Cancer Lett. 2020 Aug 22;494:132–141. doi: 10.1016/j.canlet.2020.08.019

Figure 2.

Figure 2.

Mechanisms of NUPR1-mediated Chemotherapeutic Resistance in Breast, Lung, and Colorectal Cancers. (left) NUPR1 is induced when challenged with chemotherapeutics doxorubicin and paclitaxel. NUPR1 controls p21 localization by mediating p21 phosphorylation in a PI3K/AKT-dependent manner. NUPR1 upregulates p21, which was shown to require p53 and p300, resulting in the upregulation of p21 target gene, BCL2L1 (i.e. BCL-XL). (middle) NUPR1 is induced by chemotherapeutic oxaliplatin, and induces ER stress, ROS generation, and autophagy. NUPR1 engages in a positive feedback loop with ER stress protein ATF4, and transcriptionally regulates ER stress protein CHOP. (right) NUPR1 mediates autolysosomal processing, and transcriptionally regulates SNAP25, which together with VAMP8, can impact autolysosomal efflux. NUPR1 dysregulation in cancer impacts p62, p21, and p27 expression. Created with BioRender.com.