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  1. Artikel: Unique and overlapping roles of NRF2 and NRF1 in transcriptional regulation.

    Sekine, Hiroki / Motohashi, Hozumi

    Journal of clinical biochemistry and nutrition

    2023  Band 74, Heft 2, Seite(n) 91–96

    Abstract: Transcription is regulated by specific transcription factors that mediate signaling in response to extrinsic and intrinsic stimuli such as nutrients, hormones, and oxidative stresses. Many transcription factors are grouped based on their highly conserved ...

    Abstract Transcription is regulated by specific transcription factors that mediate signaling in response to extrinsic and intrinsic stimuli such as nutrients, hormones, and oxidative stresses. Many transcription factors are grouped based on their highly conserved DNA binding domains. Consequently, transcription factors within the same family often exhibit functional redundancy and compensation. NRF2 (NFE2L2) and NRF1 (NFE2L1) belong to the CNC family transcription factors, which are responsible for various stress responses. Although their DNA binding properties are strikingly similar, NRF2 and NRF1 are recognized to play distinct roles in a cell by mediating responses to oxidative stress and proteotoxic stress, respectively. In this review, we here overview the distinct and shared roles of NRF2 and NRF1 in the transcriptional regulation of target genes, with a particular focus on the nuclear protein binding partners associated with each factor.
    Sprache Englisch
    Erscheinungsdatum 2023-11-22
    Erscheinungsland Japan
    Dokumenttyp Journal Article
    ZDB-ID 632945-7
    ISSN 1880-5086 ; 0912-0009
    ISSN (online) 1880-5086
    ISSN 0912-0009
    DOI 10.3164/jcbn.23-106
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: Roles of CNC Transcription Factors NRF1 and NRF2 in Cancer.

    Sekine, Hiroki / Motohashi, Hozumi

    Cancers

    2021  Band 13, Heft 3

    Abstract: Cancer cells exhibit unique metabolic features and take advantage of them to enhance their survival and proliferation. While the activation of NRF2 (nuclear factor erythroid 2-like 2; NFE2L2), a CNC (cap'n'collar) family transcription factor, is ... ...

    Abstract Cancer cells exhibit unique metabolic features and take advantage of them to enhance their survival and proliferation. While the activation of NRF2 (nuclear factor erythroid 2-like 2; NFE2L2), a CNC (cap'n'collar) family transcription factor, is effective for the prevention and alleviation of various diseases, NRF2 contributes to cancer malignancy by promoting aggressive tumorigenesis and conferring therapeutic resistance. NRF2-mediated metabolic reprogramming and increased antioxidant capacity underlie the malignant behaviors of NRF2-activated cancer cells. Another member of the CNC family, NRF1, plays a key role in the therapeutic resistance of cancers. Since NRF1 maintains proteasome activity by inducing proteasome subunit genes in response to proteasome inhibitors, NRF1 protects cancer cells from proteotoxicity induced by anticancer proteasome inhibitors. An important metabolite that activates NRF1 is UDP-GlcNAc (uridine diphosphate N-acetylglucosamine), which is abundantly generated in many cancer cells from glucose and glutamine via the hexosamine pathway. Thus, the metabolic signatures of cancer cells are closely related to the oncogenic and tumor-promoting functions of CNC family members. In this review, we provide a brief overview of NRF2-mediated cancer malignancy and elaborate on NRF1-mediated drug resistance affected by an oncometabolite UDP-GlcNAc.
    Sprache Englisch
    Erscheinungsdatum 2021-02-01
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13030541
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel: The KEAP1-NRF2 System in Healthy Aging and Longevity.

    Matsumaru, Daisuke / Motohashi, Hozumi

    Antioxidants (Basel, Switzerland)

    2021  Band 10, Heft 12

    Abstract: Aging is inevitable, but the inherently and genetically programmed aging process is markedly influenced by environmental factors. All organisms are constantly exposed to various stresses, either exogenous or endogenous, throughout their lives, and the ... ...

    Abstract Aging is inevitable, but the inherently and genetically programmed aging process is markedly influenced by environmental factors. All organisms are constantly exposed to various stresses, either exogenous or endogenous, throughout their lives, and the quality and quantity of the stresses generate diverse impacts on the organismal aging process. In the current oxygenic atmosphere on earth, oxidative stress caused by reactive oxygen species is one of the most common and critical environmental factors for life. The Kelch-like ECH-associated protein 1-NFE2-related factor 2 (KEAP1-NRF2) system is a critical defense mechanism of cells and organisms in response to redox perturbations. In the presence of oxidative and electrophilic insults, the thiol moieties of cysteine in KEAP1 are modified, and consequently NRF2 activates its target genes for detoxification and cytoprotection. A number of studies have clarified the contributions of the KEAP1-NRF2 system to the prevention and attenuation of physiological aging and aging-related diseases. Accumulating knowledge to control stress-induced damage may provide a clue for extending healthspan and treating aging-related diseases. In this review, we focus on the relationships between oxidative stress and aging-related alterations in the sensory, glandular, muscular, and central nervous systems and the roles of the KEAP1-NRF2 system in aging processes.
    Sprache Englisch
    Erscheinungsdatum 2021-11-30
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox10121929
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: NRF2 signalling in cytoprotection and metabolism.

    Murakami, Shohei / Kusano, Yusuke / Okazaki, Keito / Akaike, Takaaki / Motohashi, Hozumi

    British journal of pharmacology

    2023  

    Abstract: The KEAP1-NRF2 system plays a central role in cytoprotection in defence mechanisms against oxidative stress. The KEAP1-NRF2 system has been regarded as a sulfur-utilizing cytoprotective mechanism, because KEAP1 serves as a biosensor for electrophiles by ... ...

    Abstract The KEAP1-NRF2 system plays a central role in cytoprotection in defence mechanisms against oxidative stress. The KEAP1-NRF2 system has been regarded as a sulfur-utilizing cytoprotective mechanism, because KEAP1 serves as a biosensor for electrophiles by using its reactive thiols and NRF2 is a transcriptional factor regulating genes involved in sulfur-mediated redox reactions. NRF2 is a key regulator of cytoprotective genes, such as antioxidant and detoxification genes, and also possesses potent anti-inflammatory activity. Recently NRF2 has been the focus of attention as a regulator of cellular metabolism and mitochondrial function. The NRF2-mediated regulatory mechanisms of metabolites and mitochondria have been considered diverse, but have not yet been fully clarified. This review article provides an overview of molecular mechanisms that regulate NRF2 signalling and its cytoprotective roles, and highlights NRF2 contribution to cellular metabolism, particularly in the context of mitochondrial function and newly-found sulfur metabolism.
    Sprache Englisch
    Erscheinungsdatum 2023-09-15
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/bph.16246
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Genetic, metabolic and immunological features of cancers with NRF2 addiction.

    Kitamura, Hiroshi / Takeda, Haruna / Motohashi, Hozumi

    FEBS letters

    2022  Band 596, Heft 16, Seite(n) 1981–1993

    Abstract: Nuclear factor erythroid-derived 2-like 2 (NRF2) is a master transcription factor that coordinately regulates the expression of many cytoprotective genes and plays a central role in defense mechanisms against oxidative and electrophilic insults. Although ...

    Abstract Nuclear factor erythroid-derived 2-like 2 (NRF2) is a master transcription factor that coordinately regulates the expression of many cytoprotective genes and plays a central role in defense mechanisms against oxidative and electrophilic insults. Although increased NRF2 activity is principally beneficial for our health, NRF2 activation in cancer cells is detrimental. Many human cancers exhibit persistent NRF2 activation and such cancer cells rely on NRF2 for most of their malignant characteristics, such as therapeutic resistance and aggressive tumourigenesis, and thus fall into NRF2 addiction. The persistent activation of NRF2 confers great advantages on cancer cells, whereas it is not tolerated by normal cells, suggesting that certain requirements are necessary for a cell to exploit NRF2 and evolve into malignant cancer cells. In this review, recent reports and data on the genetic, metabolic and immunological features of NRF2-activated cancer cells are summarized, and prerequisites for NRF2 addiction in cancer cells and their therapeutic applications are discussed.
    Mesh-Begriff(e) Carcinogenesis ; Gene Expression Regulation ; Humans ; Kelch-Like ECH-Associated Protein 1 ; NF-E2-Related Factor 2 ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/metabolism ; Oxidation-Reduction ; Oxidative Stress
    Chemische Substanzen Kelch-Like ECH-Associated Protein 1 ; NF-E2-Related Factor 2
    Sprache Englisch
    Erscheinungsdatum 2022-08-02
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 212746-5
    ISSN 1873-3468 ; 0014-5793
    ISSN (online) 1873-3468
    ISSN 0014-5793
    DOI 10.1002/1873-3468.14458
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel: [Contribution of Nrf2 to stress response and metabolic reprogramming in cell proliferation].

    Motohashi, Hozumi

    Seikagaku. The Journal of Japanese Biochemical Society

    2014  Band 86, Heft 2, Seite(n) 269–273

    Mesh-Begriff(e) Animals ; Cell Proliferation ; Heat-Shock Proteins/metabolism ; Humans ; NF-E2-Related Factor 2/metabolism ; Neoplasms/metabolism ; Signal Transduction ; Stress, Physiological
    Chemische Substanzen Heat-Shock Proteins ; NF-E2-Related Factor 2
    Sprache Japanisch
    Erscheinungsdatum 2014-04
    Erscheinungsland Japan
    Dokumenttyp Journal Article ; Review
    ZDB-ID 282319-6
    ISSN 0037-1017
    ISSN 0037-1017
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel: The KEAP1-NRF2 System in Healthy Aging and Longevity

    Matsumaru, Daisuke / Motohashi, Hozumi

    Antioxidants. 2021 Nov. 30, v. 10, no. 12

    2021  

    Abstract: Aging is inevitable, but the inherently and genetically programmed aging process is markedly influenced by environmental factors. All organisms are constantly exposed to various stresses, either exogenous or endogenous, throughout their lives, and the ... ...

    Abstract Aging is inevitable, but the inherently and genetically programmed aging process is markedly influenced by environmental factors. All organisms are constantly exposed to various stresses, either exogenous or endogenous, throughout their lives, and the quality and quantity of the stresses generate diverse impacts on the organismal aging process. In the current oxygenic atmosphere on earth, oxidative stress caused by reactive oxygen species is one of the most common and critical environmental factors for life. The Kelch-like ECH-associated protein 1-NFE2-related factor 2 (KEAP1-NRF2) system is a critical defense mechanism of cells and organisms in response to redox perturbations. In the presence of oxidative and electrophilic insults, the thiol moieties of cysteine in KEAP1 are modified, and consequently NRF2 activates its target genes for detoxification and cytoprotection. A number of studies have clarified the contributions of the KEAP1-NRF2 system to the prevention and attenuation of physiological aging and aging-related diseases. Accumulating knowledge to control stress-induced damage may provide a clue for extending healthspan and treating aging-related diseases. In this review, we focus on the relationships between oxidative stress and aging-related alterations in the sensory, glandular, muscular, and central nervous systems and the roles of the KEAP1-NRF2 system in aging processes.
    Schlagwörter Lewis acids ; cysteine ; longevity ; oxidative stress ; reactive oxygen species ; thiols
    Sprache Englisch
    Erscheinungsverlauf 2021-1130
    Erscheinungsort Multidisciplinary Digital Publishing Institute
    Dokumenttyp Artikel
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox10121929
    Datenquelle NAL Katalog (AGRICOLA)

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  8. Artikel: Genetic, metabolic and immunological features of cancers with NRF2 addiction

    Kitamura, Hiroshi / Takeda, Haruna / Motohashi, Hozumi

    FEBS letters. 2022 Aug., v. 596, no. 16

    2022  

    Abstract: Nuclear factor erythroid‐derived 2‐like 2 (NRF2) is a master transcription factor that coordinately regulates the expression of many cytoprotective genes and plays a central role in defense mechanisms against oxidative and electrophilic insults. Although ...

    Abstract Nuclear factor erythroid‐derived 2‐like 2 (NRF2) is a master transcription factor that coordinately regulates the expression of many cytoprotective genes and plays a central role in defense mechanisms against oxidative and electrophilic insults. Although increased NRF2 activity is principally beneficial for our health, NRF2 activation in cancer cells is detrimental. Many human cancers exhibit persistent NRF2 activation and such cancer cells rely on NRF2 for most of their malignant characteristics, such as therapeutic resistance and aggressive tumourigenesis, and thus fall into NRF2 addiction. The persistent activation of NRF2 confers great advantages on cancer cells, whereas it is not tolerated by normal cells, suggesting that certain requirements are necessary for a cell to exploit NRF2 and evolve into malignant cancer cells. In this review, recent reports and data on the genetic, metabolic and immunological features of NRF2‐activated cancer cells are summarized, and prerequisites for NRF2 addiction in cancer cells and their therapeutic applications are discussed.
    Schlagwörter Lewis acids ; basic-leucine zipper transcription factors ; carcinogenesis ; humans ; therapeutics
    Sprache Englisch
    Erscheinungsverlauf 2022-08
    Umfang p. 1981-1993.
    Erscheinungsort John Wiley & Sons, Ltd
    Dokumenttyp Artikel
    Anmerkung REVIEW
    ZDB-ID 212746-5
    ISSN 1873-3468 ; 0014-5793
    ISSN (online) 1873-3468
    ISSN 0014-5793
    DOI 10.1002/1873-3468.14458
    Datenquelle NAL Katalog (AGRICOLA)

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  9. Artikel ; Online: Supersulfide biology and translational medicine for disease control.

    Barayeu, Uladzimir / Sawa, Tomohiro / Nishida, Motohiro / Wei, Fan-Yan / Motohashi, Hozumi / Akaike, Takaaki

    British journal of pharmacology

    2023  

    Abstract: For decades, the major focus of redox biology has been oxygen, the most abundant element on Earth. Molecular oxygen functions as the final electron acceptor in the mitochondrial respiratory chain, contributing to energy production in aerobic organisms. ... ...

    Abstract For decades, the major focus of redox biology has been oxygen, the most abundant element on Earth. Molecular oxygen functions as the final electron acceptor in the mitochondrial respiratory chain, contributing to energy production in aerobic organisms. In addition, oxygen-derived reactive oxygen species including hydrogen peroxide and nitrogen free radicals, such as superoxide, hydroxyl radical and nitric oxide radical, undergo a complicated sequence of electron transfer reactions with other biomolecules, which lead to their modified physiological functions and diverse biological and pathophysiological consequences (e.g. oxidative stress). What is now evident is that oxygen accounts for only a small number of redox reactions in organisms and knowledge of biological redox reactions is still quite limited. This article reviews a new aspects of redox biology which is governed by redox-active sulfur-containing molecules-supersulfides. We define the term 'supersulfides' as sulfur species with catenated sulfur atoms. Supersulfides were determined to be abundant in all organisms, but their redox biological properties have remained largely unexplored. In fact, the unique chemical properties of supersulfides permit them to be readily ionized or radicalized, thereby allowing supersulfides to actively participate in redox reactions and antioxidant responses in cells. Accumulating evidence has demonstrated that supersulfides are indispensable for fundamental biological processes such as energy production, nucleic acid metabolism, protein translation and others. Moreover, manipulation of supersulfide levels was beneficial for pathogenesis of various diseases. Thus, supersulfide biology has opened a new era of disease control that includes potential applications to clinical diagnosis, prevention and therapeutics of diseases.
    Sprache Englisch
    Erscheinungsdatum 2023-10-23
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/bph.16271
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel: Deficiency of the bZIP transcription factors Mafg and Mafk causes misexpression of genes in distinct pathways and results in lens embryonic developmental defects.

    Patel, Shaili D / Anand, Deepti / Motohashi, Hozumi / Katsuoka, Fumiki / Yamamoto, Masayuki / Lachke, Salil A

    Frontiers in cell and developmental biology

    2022  Band 10, Seite(n) 981893

    Abstract: Deficiency of the small Maf proteins Mafg and Mafk cause multiple defects, namely, progressive neuronal degeneration, cataract, thrombocytopenia and mid-gestational/perinatal lethality. Previous data ... ...

    Abstract Deficiency of the small Maf proteins Mafg and Mafk cause multiple defects, namely, progressive neuronal degeneration, cataract, thrombocytopenia and mid-gestational/perinatal lethality. Previous data shows
    Sprache Englisch
    Erscheinungsdatum 2022-08-26
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.981893
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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