Transcription Factor NRF2 Participates in Cell Cycle Progression at the Level of G1/S and Mitotic Checkpoints

Lastra, Diego; Escoll, Maribel; Cuadrado, Antonio

doi:10.3390/antiox11050946

Cited by 13 publications

(8 citation statements)

References 40 publications

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“…They found that the knockout of NRF2 in A549 and NCI-H292 cells caused cell cycle arrest in the G1 phase. Furthermore, other in vitro experiments showed that a lack of NRF2 prevented cell cycle progression and slowed cell proliferation [80,81]. Moreover, there are few reports of the relationship between NQO1 and cyclin E-CDK2.…”

Section: Discussionmentioning

confidence: 99%

The Potential Key Role of the NRF2/NQO1 Pathway in the Health Effects of Arsenic Pollution on SCC

Yang

Yan

et al. 2022

IJERPH

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Arsenic is widely present in nature and is a common environmental poison that seriously damages human health. Chronic exposure to arsenic is a major environmental poisoning factor that promotes cell proliferation and leads to malignant transformation. However, its molecular mechanism remains unclear. In this study, we found that arsenite can promote the transformation of immortalized human keratinocyte cells (HaCaT) from the G0/G1 phase to S phase and demonstrated malignant phenotypes. This phenomenon is accompanied by obviously elevated levels of NRF2, NQO1, Cyclin E, and Cyclin-dependent kinase 2 (CDK2). Silencing the NRF2 expression with small interfering RNA (siRNA) in arsenite-transformed (T-HaCaT) cells was shown to reverse the malignant phenotype. Furthermore, the siRNA silencing of NQO1 significantly decreased the levels of the cyclin E-CDK2 complex, inhibiting the G0/G1 to S phase cell cycle progression and transformation to the T-HaCaT phenotypes. Thus, we hypothesized that the NRF2/NQO1 pathway played a key role in the arsenite-induced malignancy of HaCaT cells. By increasing the expression of Cyclin E-CDK2, the NRF2/NQO1 pathway can affect cell cycle progression and cell proliferation. A new common health effect mechanism of arsenic carcinogenesis has been identified; thus, it would contribute to the development of novel treatments to prevent and treat skin cancer caused by arsenic.

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Section: Discussionmentioning

confidence: 99%

The Potential Key Role of the NRF2/NQO1 Pathway in the Health Effects of Arsenic Pollution on SCC

Yang

Yan

et al. 2022

IJERPH

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“…Recent studies have shown that PTEN-induced kinase 1 (PINK1) has a critical function in maintaining mitochondrial integrity and protecting cells from oxidative stress. Research shows that NRF2 positively influences PINK1 production and that the NRF2–PINK1 signaling pathway is critical for cell survival [ 86 ].…”

Section: Role Of Nrf2 In Senescencementioning

confidence: 99%

Electrophilic Compounds in the Human Diet and Their Role in the Induction of the Transcription Factor NRF2

Andrés,

Pérez de la Lastra,

Bustamante Munguira

et al. 2024

IJMS

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The phrase “Let food be thy medicine…” means that food can be a form of medicine and medicine can be a form of food; in other words, that the diet we eat can have a significant impact on our health and well-being. Today, this phrase is gaining prominence as more and more scientific evidence suggests that one’s diet can help prevent and treat disease. A diet rich in fruits, vegetables, whole grains, and lean protein can help reduce the risk of heart disease, cancer, diabetes, and other health problems and, on the other hand, a diet rich in processed foods, added sugars, and saturated fats can increase the risk of the same diseases. Electrophilic compounds in the diet can have a significant impact on our health, and they are molecules that covalently modify cysteine residues present in the thiol-rich Keap1 protein. These compounds bind to Keap1 and activate NRF2, which promotes its translocation to the nucleus and its binding to DNA in the ARE region, triggering the antioxidant response and protecting against oxidative stress. These compounds include polyphenols and flavonoids that are nucleophilic but are converted to electrophilic quinones by metabolic enzymes such as polyphenol oxidases (PPOs) and sulfur compounds present in foods such as the Brassica genus (broccoli, cauliflower, cabbage, Brussel sprouts, etc.) and garlic. This review summarizes our current knowledge on this subject.

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“…Recently, Lastra et al showed that NRF2 levels oscillate during cell-cycle progression, reaching a peak in G1/S and being minimal in G2/M [ 65 ] ( Figure 3 ). The decrease in NRF2 levels leads to an increase of cells in G1 as they are not ready to enter the S-phase with subsequent cycle arrest at the G1/S restriction point.…”

Section: Nrf2 Beyond Its Antioxidant Rolementioning

confidence: 99%

“…Thus, NRF2 is required for the expression of positive regulators (cyclin-dependent kinase (CDK)-2, and the transcription factor Dp-1, TFDP1) and the repression of the negative regulators cyclin dependent kinase inhibitor 1A (CDKN1A), and cyclin dependent kinase inhibitor 1B (CDKN1B) of the G1-S transition. In addition, it is also involved in the optimal expression of genes involved in DNA damage detection (cyclin-G1, CCNG1) and repair (DNA repair protein RAD51 homolog 1, RAD51) [ 65 ] ( Figure 3 ). On the other hand, as has been demonstrated in NRF2-deficient mice, a reduction in the levels of this transcription factor releases KEAP1 from its binding and allows it to bind to other proteins such as p21 at the G1/S transition [ 66 ].…”

Section: Nrf2 Beyond Its Antioxidant Rolementioning

confidence: 99%

Advances in Understanding the Role of NRF2 in Liver Pathophysiology and Its Relationship with Hepatic-Specific Cyclooxygenase-2 Expression

et al. 2023

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Oxidative stress and inflammation play an important role in the pathophysiological changes of liver diseases. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that positively regulates the basal and inducible expression of a large battery of cytoprotective genes, thus playing a key role in protecting against oxidative damage. Cyclooxygenase-2 (COX-2) is a key enzyme in prostaglandin biosynthesis. Its expression has always been associated with the induction of inflammation, but we have shown that, in addition to possessing other benefits, the constitutive expression of COX-2 in hepatocytes is beneficial in reducing inflammation and oxidative stress in multiple liver diseases. In this review, we summarized the role of NRF2 as a main agent in the resolution of oxidative stress, the crucial role of NRF2 signaling pathways during the development of chronic liver diseases, and, finally we related its action to that of COX-2, where it appears to operate as its partner in providing a hepatoprotective effect.

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Transcription Factor NRF2 Participates in Cell Cycle Progression at the Level of G1/S and Mitotic Checkpoints

Cited by 13 publications

References 40 publications

The Potential Key Role of the NRF2/NQO1 Pathway in the Health Effects of Arsenic Pollution on SCC

The Potential Key Role of the NRF2/NQO1 Pathway in the Health Effects of Arsenic Pollution on SCC

Electrophilic Compounds in the Human Diet and Their Role in the Induction of the Transcription Factor NRF2

Advances in Understanding the Role of NRF2 in Liver Pathophysiology and Its Relationship with Hepatic-Specific Cyclooxygenase-2 Expression

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