The Regulation of NRF2 by Nutrient-Responsive Signaling and Its Role in Anabolic Cancer Metabolism

被引：63

作者：

Lee, Sae Bom ^{[1
]}

Sellers, Brianna N. ^{[1
]}

DeNicola, Gina M. ^{[1
]}

机构：

[1] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Imaging & Metab, Tampa, FL 33612 USA

来源：

ANTIOXIDANTS & REDOX SIGNALING | 2018年 / 29卷 / 17期

关键词：

NRF2; KEAP1; metabolism; serine; glycine; cysteine; TRANSCRIPTION FACTOR NRF2; UNFOLDED PROTEIN RESPONSE; RENAL-CELL CARCINOMA; NRF2-MEDIATED ANTIOXIDANT RESPONSE; GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; ONE-CARBON METABOLISM; AMINO-ACID-TRANSPORT; MAMMALIAN-CELLS; GENE-EXPRESSION; HEPATOCELLULAR-CARCINOMA;

D O I：

10.1089/ars.2017.7356

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Significance: The stress responsive transcription factor nuclear factor erythroid 2 p45-related factor 2, or NRF2, regulates the expression of many cytoprotective enzymes to mitigate oxidative stress under physiological conditions. NRF2 is activated in response to oxidative stress, growth factor signaling, and changes in nutrient status. In addition, somatic mutations that disrupt the interaction between NRF2 and its negative regulator Kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated 1 (KEAP1) commonly occur in cancer and are thought to promote tumorigenesis. Recent Advances: While it is well established that aberrant NRF2 activation results in enhanced antioxidant capacity in cancer cells, recent exciting findings demonstrate a role for NRF2-mediated metabolic deregulation that supports cancer cell proliferation. Critical Issues: In this review, we describe how the NRF2-KEAP1 signaling pathway is altered in cancer, how NRF2 is regulated by changes in cellular metabolism, and how NRF2 reprograms cellular metabolism to support proliferation. Future Directions: Future studies will delineate the NRF2-regulated processes critical for metabolic adaptation to nutrient availability, cellular proliferation, and tumorigenesis.

引用

页码：1774 / 1791

页数：18

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