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NUPR1: A Critical Regulator of the Antioxidant System

Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, 163 Avenue de Luminy, 13288 Marseille, France
Author to whom correspondence should be addressed.
Academic Editors: Jacques Pouyssegur, Milica Vucetic and Fatima Mechta-Grigoriou
Cancers 2021, 13(15), 3670;
Received: 20 May 2021 / Revised: 18 July 2021 / Accepted: 20 July 2021 / Published: 22 July 2021
(This article belongs to the Special Issue Metabolic Pathways and Redox Homeostasis in Cancer)
Nuclear protein 1 (NUPR1) is activated in cellular stress and is expressed at high levels in cancer cells. Much evidence has been gathered supporting its critical role in regulating the antioxidant system. Our review aims to summarize the literature data on the impact of NUPR1 on the oxidative stress response via such a regulatory role and how its inhibition induces reactive oxygen species-mediated cell death, such as ferroptosis.
Nuclear protein 1 (NUPR1) is a small intrinsically disordered protein (IDP) activated in response to various types of cellular stress, including endoplasmic reticulum (ER) stress and oxidative stress. Reactive oxygen species (ROS) are mainly produced during mitochondrial oxidative metabolism, and directly impact redox homeostasis and oxidative stress. Ferroptosis is a ROS-dependent programmed cell death driven by an iron-mediated redox reaction. Substantial evidence supports a maintenance role of the stress-inducible protein NUPR1 on cancer cell metabolism that confers chemotherapeutic resistance by upregulating mitochondrial function-associated genes and various antioxidant genes in cancer cells. NUPR1, identified as an antagonist of ferroptosis, plays an important role in redox reactions. This review summarizes the current knowledge on the mechanism behind the observed impact of NUPR1 on mitochondrial function, energy metabolism, iron metabolism, and the antioxidant system. The therapeutic potential of genetic or pharmacological inhibition of NUPR1 in cancer is also discussed. Understanding the role of NUPR1 in the antioxidant system and the mechanisms behind its regulation of ferroptosis may promote the development of more efficacious strategies for cancer therapy. View Full-Text
Keywords: NUPR1; cell death; ferroptosis; ROS; cell stress NUPR1; cell death; ferroptosis; ROS; cell stress
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MDPI and ACS Style

Huang, C.; Santofimia-Castaño, P.; Iovanna, J. NUPR1: A Critical Regulator of the Antioxidant System. Cancers 2021, 13, 3670.

AMA Style

Huang C, Santofimia-Castaño P, Iovanna J. NUPR1: A Critical Regulator of the Antioxidant System. Cancers. 2021; 13(15):3670.

Chicago/Turabian Style

Huang, Can, Patricia Santofimia-Castaño, and Juan Iovanna. 2021. "NUPR1: A Critical Regulator of the Antioxidant System" Cancers 13, no. 15: 3670.

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