Small Maf Proteins in Mammalian Gene Control: Mere Dimerization Partners or Dynamic Transcriptional Regulators?

Blank, Volker

doi:10.1016/j.jmb.2007.11.074

Cited by 138 publications

(116 citation statements)

References 117 publications

(161 reference statements)

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“…Nrf1 and Nrf2 are members of the Cap'n'Collar (CNC) family of transcription factors and both of them bind to ARE (Motohashi et al, 2002;Blank, 2008). Because of the similarity in binding specificity and expression profile between Nrf1 and Nrf2, they are supposed to share overlapping target genes and overlapping functions.…”

Section: Discussionmentioning

confidence: 99%

Pyrroloquinoline quinone rescues hippocampal neurons from glutamate-induced cell death through activation of Nrf2 and up-regulation of antioxidant genes

Zhang¹,

Ding²,

Gao³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. Pyrroloquinoline quinone (PQQ) has been shown to protect primary cultured hippocampal neurons from glutamateinduced cell apoptosis by scavenging reactive oxygen species (ROS) and activating phosphatidylinositol-3-kinase (PI3K)/Akt signaling. We investigated the downstream pathways of PI3K/Akt involved in PQQ protection of glutamate-injured hippocampal neurons. Western blot analysis indicated that PQQ treatment following glutamate stimulation triggers phosphorylation of glycogen synthase kinase 3β, accompanied by maintenance of Akt activation. Immunostaining and quantitative RT-PCR revealed that PQQ treatment promotes nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), and up-regulates mRNA expression of Nrf2 and the antioxidant enzyme genes, heme oxygenase-1 and glutamate cysteine ligase catalytic in glutamate-injured hippocampal neurons; this is a process dependent on the PI3K/Akt pathway, as evidenced by blocking experiments with PI3K inhibitors. In addition, increased ROS production and decreased glutathione ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (3): 2652-2664 (2012) PQQ rescues neurons from death through Nrf2 activation 2653 levels in glutamate-injured hippocampal neurons were found to be reduced by PQQ treatment. Collectively, our findings suggest that PQQ exerts neuroprotective activity, possibly through PI3K/Akt-dependent activation of Nrf2 and up-regulation of antioxidant genes. However, the ability of PQQ to scavenge ROS was not totally regulated by PI3K/Akt signaling; possibly it is governed by other mechanisms.

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Section: Discussionmentioning

confidence: 99%

Pyrroloquinoline quinone rescues hippocampal neurons from glutamate-induced cell death through activation of Nrf2 and up-regulation of antioxidant genes

Zhang¹,

Ding²,

Gao³

et al. 2012

Genet. Mol. Res.

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“…The Maf family proteins belong to the basic leucine zipper transcription factors, including c-Maf, MafA, MafB, MafF, MafG, MafK, and Nrl, 1,2 of which c-Maf, MafA, and MafB belong to the large Maf subgroup containing the complete structure of a transcription factor, including a basic DNA-binding domain, a leucine zipper structure, and an activation domain. 2 In the fetus, c-Maf is involved in the development of several organs and tissues, including islets.…”

Section: Introductionmentioning

confidence: 99%

“…2 In the fetus, c-Maf is involved in the development of several organs and tissues, including islets. 1 In the adult, c-Maf is associated with the differentiation of helper T cells, including Th2, and Th17.…”

Section: Introductionmentioning

confidence: 99%

The ubiquitin ligase HERC4 mediates c-Maf ubiquitination and delays the growth of multiple myeloma xenografts in nude mice

Zhang

Tong

Tang

et al. 2016

Blood

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Key Points• HERC4 is the first identified ubiquitin ligase that mediates c-Maf ubiquitination and degradation.• HERC4 suppresses MM cell proliferation and delays MM tumor growth.The transcription factor c-Maf is extensively involved in the pathophysiology of multiple myeloma (MM), a fatal malignancy of plasma cells. In the present study, affinity chromatography and mass spectrometry were used to identify c-Maf ubiquitination-associated proteins, from which the E3 ligase HERC4 was found to interact with c-Maf and catalyzed its polyubiquitination and subsequent proteasome-mediated degradation. HERC4 mediated polyubiquitination at K85 and K297 in c-Maf, and this polyubiquitination could be prevented by the isopeptidase USP5. Further analysis on the NCI-60 cell line collection revealed that RPMI 8226, a MM-derived cell line, expressed the lowest level of HERC4. Primary bone marrow analysis revealed HERC4 expression was high in normal bone marrow, but was steadily decreased during myelomagenesis. These findings suggested HERC4 played an important role in MM progression. Moreover, ectopic HERC4 expression decreased MM proliferation in vitro, and delayed xenograft tumor growth in vivo. Therefore, modulation of c-Maf ubiquitination by targeting HERC4 may represent a new therapeutic modality for MM. (Blood. 2016;127(13):1676-1686

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“…13 For instance, although the co-occupancy of p45 and MafK at genome elements activates transcription, binding of a Bach1 and MafK heterodimer to these elements results in gene repression. 14 Many different CNC and Maf heterodimers are formed, 15 causing the biology of CNC and Maf members to be complex. Although Nrf1 Ϫ/Ϫ mice are anemic and have embryonic or postnatal lethality, 16 ablation of p45 in mice leads to defective platelet production.…”

Section: Introductionmentioning

confidence: 99%

“…22,23 The CNC/Maf network has been associated with a myriad of human disorders, including those of the skin, respiratory system, and hematopoietic system. 10,15,24 Thus, drug therapy involving the CNC pathway is actively being studied in humans for cancer chemoprevention, inflammatory diseases, and autoimmune diseases (for review, see Sykiotis and Bohmann 10 ). For example, the fumaric acid ester dimethylfumarate, which exerts neuroprotection by inducing Nrf2 expression, is currently in a phase 3 clinical trial as an orally active effective treatment of human multiple sclerosis with limited side effects.…”

mentioning

confidence: 99%

Regulation of APC development, immune response, and autoimmunity by Bach1/HO-1 pathway in mice

Garcia-Flores

Minisandram

et al. 2012

Blood

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IntroductionAbnormal development of APCs can result in immunodeficiency and autoimmune disease. APCs, which include macrophages, B cells, and dendritic cells (DCs), and are critical for mediating adaptive immunity to foreign antigens as well as inducing tolerance to self-antigens. At steady state, macrophages are generated from monocytes, and classic DCs are derived from their precursor (pre-cDCs) and common DC progenitors (CDPs). [1][2][3][4][5][6] These cells are all generated from upstream macrophage-DC precursor (MDP) cells, 7-9 which are themselves derived from less lineage-restricted common myeloid progenitors (CMPs). 1 The entire populations of hematopoietic cells originate from pluripotent HSCs in the BM (see Figure 7A). Despite recent advances, the cellular factors that regulate the progression of HSCs to the development of APCs remain largely uncharacterized.Cap 'n' collar (CNC) proteins are evolutionarily conserved factors that are known to be essential for the resolution of oxidative stress. 10 In Caenorhabditis elegans, the CNC protein SKN-1 regulates longevity. 11,12 In mammals, there are 6 members within the CNC family (p45, Nrf1, Nrf2, Nrf3, Bach1, and Bach2) that heterodimerize with small Maf proteins (MafK, MafG, and MafF) to direct either gene induction or repression. 13 For instance, although the co-occupancy of p45 and MafK at genome elements activates transcription, binding of a Bach1 and MafK heterodimer to these elements results in gene repression. 14 Many different CNC and Maf heterodimers are formed, 15 causing the biology of CNC and Maf members to be complex. Although Nrf1 Ϫ/Ϫ mice are anemic and have embryonic or postnatal lethality, 16 ablation of p45 in mice leads to defective platelet production. 17 Although deletion of Bach2 in mice caused impaired antibody class switching, 18 disruption of Nrf2 resulted in a neurodegenerative disorder and autoimmune disease. [19][20][21] Deciphering the physiologic role of some of the CNC/Maf proteins has also proven to be challenging because of the potential functional redundancy among them. 22,23 The CNC/Maf network has been associated with a myriad of human disorders, including those of the skin, respiratory system, and hematopoietic system. 10,15,24 Thus, drug therapy involving the CNC pathway is actively being studied in humans for cancer chemoprevention, inflammatory diseases, and autoimmune diseases (for review, see Sykiotis and Bohmann 10 ). For example, the fumaric acid ester dimethylfumarate, which exerts neuroprotection by inducing Nrf2 expression, is currently in a phase 3 clinical trial as an orally active effective treatment of human multiple sclerosis with limited side effects. 25,26 Thus, deciphering the functions of the individual CNC subunits will not only be crucial to unraveling the overlapping and unique functions of these proteins but also provide insights to the potential of targeting CNC proteins for therapy against relevant diseases. In particular, the CNC member Bach1 is up-regulated in fetal Down syndrome (DS) brain. ...

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Small Maf Proteins in Mammalian Gene Control: Mere Dimerization Partners or Dynamic Transcriptional Regulators?

Cited by 138 publications

References 117 publications

Pyrroloquinoline quinone rescues hippocampal neurons from glutamate-induced cell death through activation of Nrf2 and up-regulation of antioxidant genes

Pyrroloquinoline quinone rescues hippocampal neurons from glutamate-induced cell death through activation of Nrf2 and up-regulation of antioxidant genes

The ubiquitin ligase HERC4 mediates c-Maf ubiquitination and delays the growth of multiple myeloma xenografts in nude mice

Regulation of APC development, immune response, and autoimmunity by Bach1/HO-1 pathway in mice

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