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1.
Genes Dev ; 33(17-18): 1252-1264, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31395740

RESUMO

Although MAX is regarded as an obligate dimerization partner for MYC, its function in normal development and neoplasia is poorly defined. We show that B-cell-specific deletion of Max has a modest effect on B-cell development but completely abrogates Eµ-Myc-driven lymphomagenesis. While Max loss affects only a few hundred genes in normal B cells, it leads to the global down-regulation of Myc-activated genes in premalignant Eµ-Myc cells. We show that the balance between MYC-MAX and MNT-MAX interactions in B cells shifts in premalignant B cells toward a MYC-driven transcriptional program. Moreover, we found that MAX loss leads to a significant reduction in MYC protein levels and down-regulation of direct transcriptional targets, including regulators of MYC stability. This phenomenon is also observed in multiple cell lines treated with MYC-MAX dimerization inhibitors. Our work uncovers a layer of Myc autoregulation critical for lymphomagenesis yet partly dispensable for normal development.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica , Linfoma/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Carcinogênese/efeitos dos fármacos , Linhagem Celular Tumoral , Inibidores Enzimáticos/farmacologia , Deleção de Genes , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Indóis/farmacologia , Cinurenina/genética , Cinurenina/metabolismo , Linfoma/fisiopatologia , Camundongos , Organoides/crescimento & desenvolvimento , Organoides/fisiopatologia , Oximas/farmacologia , Sulfonamidas/farmacologia
2.
J Agric Food Chem ; 67(32): 8783-8793, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31310107

RESUMO

Red-fleshed apples are popular as a result of their high anthocyanin content. MdMYB10 and its homologues are known to be important regulators of anthocyanin synthesis in apple, but the roles of other transcription factors are not well-understood. Here, we explored the role of MdWRKY11 in regulating anthocyanin synthesis in apple flesh. Overexpression of MdWRKY11 in apple callus could significantly promote anthocyanin accumulation, and the expression of some MYB transcription factors and structural genes increased significantly. In binding analyses, MdWRKY11 bound to W-box cis-elements in the promoters of MdMYB10, MdMYB11, and MdUFGT. However, MdWRKY11 did not interact with MdMYB10, MdbHLH3, or MdWD40 proteins, the members of the MBW complex. Sequence analyses revealed that another W-box cis-element was present in the promoter of MdHY5 (encoding a photoresponse factor), and MdWRKY11 was able to bind to the promoter of MdHY5 and promote its activity. Our findings clarify the role of MdWRKY11 in anthocyanin synthesis in red-fleshed apple and imply that other novel genes may be involved in anthocyanin synthesis.


Assuntos
Antocianinas/biossíntese , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Regulação da Expressão Gênica de Plantas , Malus/metabolismo , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Frutas/genética , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Malus/genética , Malus/crescimento & desenvolvimento , Proteínas de Plantas/genética , Fatores de Transcrição/genética
3.
Plant Mol Biol ; 101(1-2): 113-127, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31300998

RESUMO

Transcriptional regulation is an essential molecular machinery in controlling gene expression in diverse plant developmental processes including fruit ripening. This involves the interaction of transcription factors (TFs) and promoters of target genes. In banana, although a number of fruit ripening-associated TFs have been characterized, their number is relatively small. Here we identified a nuclear-localized basic leucine zipper (bZIP) TF, MabZIP93, associated with banana ripening. MabZIP93 activated cell wall modifying genes MaPL2, MaPE1, MaXTH23 and MaXGT1 by directly binding to their promoters. Transient over-expression of MabZIP93 in banana fruit resulted in the increased expression of MaPL2, MaPE1, MaXTH23 and MaXGT1. Moreover, a mitogen-activated protein kinase MaMPK2 and MabZIP93 were found to interact with MabZIP93. The interaction of MabZIP93 with MaMPK2 enhanced MabZIP93 activation of cell wall modifying genes, which was likely due to the phosphorylation of MabZIP93 mediated by MaMPK2. Overall, this study shows that MaMPK2 interacts with and phosphorylates MabZIP93 to promote MabZIP93-mediated transcriptional activation of cell wall modifying genes, thereby expanding our understanding of gene networks associated with banana fruit ripening.


Assuntos
Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes/genética , Musa/genética , Proteínas de Plantas/metabolismo , Ativação Transcricional , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Núcleo Celular/metabolismo , Parede Celular/metabolismo , Frutas/genética , Musa/fisiologia , Fosforilação , Proteínas de Plantas/genética , Regiões Promotoras Genéticas/genética
4.
Life Sci ; 232: 116626, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276688

RESUMO

PURPOSE: The aim of this study was to investigate the role of the suppressor of activator protein-1 regulated by interferon (SARI), in the development and progression of prostate cancer. METHODS: Sixty-seven prostate cancer tissue specimens and 20 benign prostatic hyperplasia specimens were used to investigate the correlation between SARI expression and clinicopathologic parameters. Immunohistochemistry was used to detect the SARI and E-cadherin protein expression in the prostate cancer and benign prostatic hyperplasia specimens, and their correlation was established. Quantitative PCR (qPCR) was used to determine the SARI mRNA expression in a normal prostate cell line (RWPE-1) and prostate cancer cell lines (LNCaP and PC3). Western blotting was used to detect the SARI protein expression in the RWPE-1, LNCaP, and PC3 cell lines. RESULTS: SARI protein expression did not correlate with the prostate cancer patients' age or serum Prostate-Specific Antigen value but did show a correlation with the tumor stage of prostate cancer and Gleason score. SARI and E-cadherin expression in the prostate cancer tissue was significantly lower than in the benign prostatic hyperplasia specimens, suggesting a positive correlation between the SARI and E-cadherin expression. SARI mRNA and protein were highly expressed in RWPE-1, the normal prostate cell line, but SARI mRNA and protein expression were reduced in the prostate cancer cell lines, LNCaP and PC3. Significant differences in the expression were found between the prostate cancer cell lines and the normal prostate cell line. CONCLUSION: In this study, high SARI expression was found to be negatively correlated with the development and progression of prostate cancer.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Neoplasias da Próstata/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Idoso , Western Blotting , Caderinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Imuno-Histoquímica , Interferons/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Fosfatidilinositol 3-Quinases/metabolismo , Próstata/citologia , Próstata/patologia , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , Fator de Transcrição AP-1/metabolismo , beta Catenina/metabolismo
5.
Chem Biol Interact ; 309: 108706, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31194955

RESUMO

Oxidative-stress-induced osteoblast dysfunction plays an important role in the development and progression of osteoporosis. BTB and CNC homology 1 (Bach1) has been suggested as a critical regulator of oxidative stress; however, whether Bach1 plays a role in regulating oxidative-stress-induced osteoblast dysfunction remains unknown. Thus, we investigated the potential role and mechanism of Bach1 in regulating oxidative-stress-induced osteoblast dysfunction. Osteoblasts were treated with hydrogen peroxide (H2O2) to mimic a pathological environment for osteoporosis in vitro. H2O2 exposure induced Bach1 expression in osteoblasts. Functional experiments demonstrated that Bach1 silencing improved cell viability and reduced cell apoptosis and reactive oxygen species (ROS) production in H2O2-treated cells, while Bach1 overexpression produced the opposite effects. Notably, Bach1 inhibition upregulated alkaline phosphatase activity and osteoblast mineralization. Mechanism research revealed that Bach1 inhibition increased the activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling and upregulated heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1 mRNA expression. The Bach1 inhibition-mediated protective effect was partially reversed by silencing Nrf2 in H2O2-exposed osteoblasts. Taken together, these results demonstrate that Bach1 inhibition alleviates oxidative-stress-induced osteoblast apoptosis and dysfunction by enhancing Nrf2/ARE signaling activation, findings that suggest a critical role for the Bach1/Nrf2/ARE regulation axis in osteoporosis progression. Our study suggests that Bach1 may serve as a potential therapeutic target for treating osteoporosis.


Assuntos
Elementos de Resposta Antioxidante/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Peróxido de Hidrogênio/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Fatores de Transcrição de Zíper de Leucina Básica/antagonistas & inibidores , Fatores de Transcrição de Zíper de Leucina Básica/genética , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Camundongos , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/genética , Osteoblastos/citologia , Osteoblastos/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo
6.
J Agric Food Chem ; 67(26): 7390-7398, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31244202

RESUMO

Wound-induced suberization is an essentially protective healing process for wounded fruit to reduce water loss and microbial infection. It has been demonstrated that abscisic acid (ABA) could promote wound suberization, but the molecular mechanism of ABA regulation remains little known. In this study, the transcript level of Achn030011 (designated as AchnKCS), coding a ß-ketoacyl-coenzyme A synthase (KCS) involved in suberin biosynthesis, was found to be significantly upregulated by ABA in wounded kiwifruit. A bZIP transcription factor (Achn270881), a possible downstream transcription factor in the ABA signaling pathway, was screened and designated as AchnbZIP12 according to its homology with related Arabidopsis transcription factors. A yeast one-hybrid assay demonstrated that AchnbZIP12 could interact with the AchnKCS promoter. Furthermore, significant trans-activation of AchnbZIP12 on AchnKCS was verified. The transcript level of AchnbZIP12 was also upregulated upon treatment with ABA. These results imply that AchnbZIP12 acts as a positive regulator in ABA-mediated AchnKCS transcription during wound suberization of kiwifruit.


Assuntos
Ácido Abscísico/farmacologia , Actinidia/efeitos dos fármacos , Actinidia/fisiologia , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Reguladores de Crescimento de Planta/farmacologia , Proteínas de Plantas/genética , Actinidia/genética , Fatores de Transcrição de Zíper de Leucina Básica/genética , Frutas/efeitos dos fármacos , Frutas/genética , Frutas/fisiologia , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas/efeitos dos fármacos
7.
BMC Genomics ; 20(1): 483, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185893

RESUMO

BACKGROUND: In reported plants, the bZIP family is one of the largest transcription factor families. bZIP genes play roles in the light signal, seed maturation, flower development, cell elongation, seed accumulation protein, abiotic and biological stress and other biological processes. While, no detailed identification and genome-wide analysis of bZIP family genes in Fagopyum talaricum (tartary buckwheat) has previously been published. The recently reported genome sequence of tartary buckwheat provides theoretical basis for us to study and discuss the characteristics and expression of bZIP genes in tartary buckwheat based on the whole genome. RESULTS: In this study, 96 FtbZIP genes named from FtbZIP1 to FtbZIP96 were identified and divided into 11 subfamilies according to their genetic relationship with 70 bZIPs of A. thaliana. FtbZIP genes are not evenly distributed on the chromosomes, and we found tandem and segmental duplication events of FtbZIP genes on 8 tartary buckwheat chromosomes. According to the results of gene and motif composition, FtbZIP located in the same group contained analogous intron/exon organizations and motif composition. By qRT-PCR, we quantified the expression of FtbZIP members in stem, root, leaf, fruit, and flower and during fruit development. Exogenous ABA treatment increased the weight of tartary buckwheat fruit and changed the expressions of FtbZIP genes in group A. CONCLUSIONS: Through our study, we identified 96 FtbZIP genes in tartary buckwheat and synthetically further analyzed the structure composition, evolution analysis and expression pattern of FtbZIP proteins. The expression pattern indicates that FtbZIP is important in the course of plant growth and development of tartary buckwheat. Through comprehensively analyzing fruit weight and FtbZIP genes expression after ABA treatment and endogenous ABA content of tartary buckwheat fruit, ABA may regulate downstream gene expression by regulating the expression of FtPinG0003523300.01 and FtPinG0003196200.01, thus indirectly affecting the fruit development of tartary buckwheat. This will help us to further study the function of FtbZIP genes in the tartary buckwheat growth and improve the fruit of tartary buckwheat.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Evolução Molecular , Fagopyrum/genética , Perfilação da Expressão Gênica , Genômica , Filogenia , Cromossomos de Plantas/genética , Sequência Conservada , Fagopyrum/crescimento & desenvolvimento , Frutas/crescimento & desenvolvimento , Duplicação Gênica , Genoma de Planta/genética , Motivos de Nucleotídeos , Especificidade de Órgãos
8.
BMC Plant Biol ; 19(1): 260, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208338

RESUMO

BACKGROUND: Drought is a major abiotic stress factor that influences the yield of crops. Basic leucine zipper motif (bZIP) transcription factors play an important regulatory role in plant drought stress responses. However, the functions of a number of bZIP transcription factors in rice are still unknown. RESULTS: In this study, a novel drought stress-related bZIP transcription factor, OsbZIP62, was identified in rice. This gene was selected from a transcriptome analysis of several typical rice varieties with different drought tolerances. OsbZIP62 expression was induced by drought, hydrogen peroxide, and abscisic acid (ABA) treatment. Overexpression of OsbZIP62-VP64 (OsbZIP62V) enhanced the drought tolerance and oxidative stress tolerance of transgenic rice, while osbzip62 mutants exhibited the opposite phenotype. OsbZIP62-GFP was localized to the nucleus, and the N-terminal sequence (amino acids 1-68) was necessary for the transcriptional activation activity of OsbZIP62. RNA-seq analysis showed that the expression of many stress-related genes (e.g., OsGL1, OsNAC10, and DSM2) was upregulated in OsbZIP62V plants. Moreover, OsbZIP62 could bind to the promoters of several putative target genes and could interact with stress/ABA-activated protein kinases (SAPKs). CONCLUSIONS: OsbZIP62 is involved in ABA signalling pathways and positively regulates rice drought tolerance by regulating the expression of genes associated with stress, and this gene could be used for the genetic modification of crops with improved drought tolerance.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/fisiologia , Oryza/genética , Proteínas de Plantas/genética , Fatores de Transcrição de Zíper de Leucina Básica/genética , Desidratação , Regulação da Expressão Gênica de Plantas , Técnicas de Silenciamento de Genes , Oryza/fisiologia , Estresse Oxidativo , Proteínas de Plantas/fisiologia , Plantas Geneticamente Modificadas
9.
Gut ; 68(10): 1858-1871, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31118247

RESUMO

BACKGROUND AND AIMS: The unique expression pattern makes oncofetal proteins ideal diagnostic biomarkers and therapeutic targets in cancer. However, few oncofetal proteins have been identified and entered clinical practice. METHODS: Fetal liver, adult liver and hepatocellular carcinoma (HCC) tissues were employed to assess the expression of hepatic leukaemia factor (HLF). The impact of HLF on HCC onset and progression was investigated both in vivo and in vitro. The association between HLF and patient prognosis was determined in patient cohorts. The correlation between HLF expression and sorafenib benefits in HCC was further evaluated in patient cohorts and patient-derived xenografts (PDXs). RESULTS: HLF is a novel oncofetal protein which is reactivated in HCC by SOX2 and OCT4. Functional studies revealed that HLF transactivates c-Jun to promote tumour initiating cell (TIC) generation and enhances TIC-like properties of hepatoma cells, thus driving HCC initiation and progression. Consistently, our clinical investigations elucidated the association between HLF and patient prognosis and unravelled the close correlation between HLF levels and c-Jun expression in patient HCCs. Importantly, HLF/c-Jun axis determines the responses of hepatoma cells to sorafenib treatment, and interference of HLF abrogated c-Jun activation and enhanced sorafenib response. Analysis of patient cohorts and PDXs further suggests that HLF/c-Jun axis might serve as a biomarker for sorafenib benefits in HCC patients. CONCLUSIONS: Our findings uncovered HLF as a novel oncofetal protein and revealed the crucial role of the HLF/c-Jun axis in HCC development and sorafenib response, rendering HLF as an optimal target for the prevention and intervention of HCC.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Carcinoma Hepatocelular/genética , Resistencia a Medicamentos Antineoplásicos , Genes jun/genética , Neoplasias Hepáticas/genética , Sorafenibe/farmacologia , Adulto , Antineoplásicos/farmacologia , Apoptose , Fatores de Transcrição de Zíper de Leucina Básica/biossíntese , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , DNA de Neoplasias/genética , Progressão da Doença , Feminino , Humanos , Imunoprecipitação , Zíper de Leucina , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Prognóstico
10.
Int J Mol Sci ; 20(9)2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31060272

RESUMO

The basic leucine zipper (bZIP) transcription factor (TF) family is one of the largest gene families, and play crucial roles in many processes, including stress responses, hormone effects. The TF family also participates in plant growth and development. However, limited information is available for these genes in moso bamboo (Phyllostachys edulis), one of the most important non-timber forest products in the world. In the present study, 154 putative PhebZIP genes were identified in the moso bamboo genome. The phylogenetic analyses indicate that the PhebZIP gene proteins classify into 9 subfamilies and the gene structures and conserved motifs that analyses identified among all PhebZIP proteins suggested a high group-specificity. Microsynteny and evolutionary patterns analyses of the non-synonymous (Ka) and synonymous (Ks) substitution rates and their ratios indicated that paralogous pairs of PhebZIP genes in moso bamboo underwent a large-scale genome duplication event that occurred 7-15 million years ago (MYA). According to promoter sequence analysis, we further selected 18 genes which contain the higher number of cis-regulatory elements for expression analysis. The result showed that these genes are extensively involved in GA-, ABA- and MeJA-responses, with possibly different mechanisms. The tissue-specific expression profiles of PhebZIP genes in five plant tissues/organs/developmental stages suggested that these genes are involved in moso bamboo organ development, especially seed development. Subcellular localization and transactivation activity analysis showed that PhebZIP47 and PhebZIP126 were localized in the nucleus and PhebZIP47 with no transcriptional activation in yeast. Our research provides a comprehensive understanding of PhebZIP genes and may aid in the selection of appropriate candidate genes for further cloning and functional analysis in moso bamboo growth and development, and improve their resistance to stress during their life.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Estudo de Associação Genômica Ampla , Sasa/genética , Motivos de Aminoácidos , Sequência de Aminoácidos , Fatores de Transcrição de Zíper de Leucina Básica/química , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Mapeamento Cromossômico , Biologia Computacional , Sequência Conservada , Evolução Molecular , Perfilação da Expressão Gênica , Filogenia , Sequências Reguladoras de Ácido Nucleico , Sasa/classificação , Sasa/metabolismo , Transcriptoma
11.
Plant Sci ; 283: 407-415, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31128711

RESUMO

Starch content and composition are major determinants of yield and quality in maize. In recent years, the major genes for starch metabolism have been cloned in this species. However, the role of transcription factors in regulating the starch metabolism pathway remains unclear. The ZmbZIP22 gene encodes a bZIP transcription factor. In our study, plants overexpressing ZmbZIP22 showed reductions in the size of starch granules, the size and weight of seeds, reduced amylose content, and alterations in the chemical structure of starch granules. Also, overexpression of ZmbZIP22 resulted in increases in the contents of soluble sugars and reducing sugars in transgenic rice and maize. ZmbZIP22 promotes the transcription of starch metabolism genes by binding to their promoters. Screening by yeast one-hybrid assays indicated a possible interaction between ZmbZIP22 and the promoters of eight key starch enzyme genes. Collectively, our results indicated that ZmbZIP22 functions as a negative regulator of starch synthesis, and suggest that this occurs through the regulation of key sugar and starch metabolism genes in maize.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Endosperma/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Amido/metabolismo , Zea mays/metabolismo , Amilose/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Southern Blotting , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Análise de Sequência de DNA , Transcriptoma , Técnicas do Sistema de Duplo-Híbrido , Zea mays/genética
12.
Int J Mol Sci ; 20(7)2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30987332

RESUMO

Basic leucine zipper transcription factor ATF-like (BATF)-3, belonging to activator protein 1 (AP-1) superfamily transcription factors, is essential for homeostatic development of CD8α⁺ classical dendritic cells activating CD8 T-cell responses to intracellular pathogens. In this study, the characteristics and cDNA cloning of the CiBATF3 molecule were described in grass carp (Ctenopharyngodon idella). CiBATF3 had abundant expression in immune-related organizations, including liver, spleen and gill, and grass carp reovirus (GCRV) infection had significantly changed its expression level. After Ctenopharyngodon idella kidney (CIK) cells were challenged with pathogen-associated molecular patterns (PAMPs), polyinosinic:polycytidylic acid (poly(I:C)) stimulation induced higher mRNA levels of CiBATF3 than that of lipopolysaccharide (LPS). Subcellular localization showed that CiBATF3-GFP was entirely distributed throughout cells and nuclear translocation of CiBATF3 was found after poly(I:C) treatment. Additionally, the interaction between CiBATF3 and interleukin 10 (IL-10) was proven by bimolecular fluorescence complementation (BiFC) system. The small interfering RNA (siRNA)-mediated CiBATF3 silencing showed that the mRNA of CiBATF3 and its downstream genes were down-regulated in vitro and in vivo. CiBATF3 played a negative regulatory role in the transcriptional activities of AP-1 and NF-κB reporter gene. In summary, the results may provide valuable information on fundamental functional mechanisms of CiBATF3.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Carpas/metabolismo , Imunidade Inata/fisiologia , Infecções por Reoviridae/imunologia , Animais , Fatores de Transcrição de Zíper de Leucina Básica/genética , Linfócitos T CD8-Positivos/metabolismo , Regulação da Expressão Gênica , Inativação Gênica , Imunidade Inata/genética , Lipopolissacarídeos/farmacologia , Fator de Transcrição AP-1/metabolismo
13.
Nat Commun ; 10(1): 1569, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30952851

RESUMO

Charting a temporal path in gene networks requires linking early transcription factor (TF)-triggered events to downstream effects. We scale-up a cell-based TF-perturbation assay to identify direct regulated targets of 33 nitrogen (N)-early response TFs encompassing 88% of N-responsive Arabidopsis genes. We uncover a duality where each TF is an inducer and repressor, and in vitro cis-motifs are typically specific to regulation directionality. Validated TF-targets (71,836) are used to refine precision of a time-inferred root network, connecting 145 N-responsive TFs and 311 targets. These data are used to chart network paths from direct TF1-regulated targets identified in cells to indirect targets responding only in planta via Network Walking. We uncover network paths from TGA1 and CRF4 to direct TF2 targets, which in turn regulate 76% and 87% of TF1 indirect targets in planta, respectively. These results have implications for N-use and the approach can reveal temporal networks for any biological system.


Assuntos
Arabidopsis/genética , Redes Reguladoras de Genes , Nitrogênio/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/fisiologia , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/fisiologia , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/fisiologia
14.
Int J Mol Sci ; 20(6)2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30901838

RESUMO

As core components of ABA signaling pathway, SnRK2s (Sucrose nonfermenting1⁻Related protein Kinase 2) bind to and phosphorylate AREB/ABF (ABA responsive element binding protein/ABRE-binding factor) transcriptional factors, particularly bZIPs (basic region-leucine zipper), to participate in various biological processes, including flowering. Rice contains 10 SnRK2 members denoted as SAPK1-10 (Stress-Activated Protein Kinase) and dozens of bZIPs. However, which of the SAPKs and bZIPs pair and involve in ABA signaling remains largely unknown. In this study, we carried out a systematical protein-protein interactomic analysis of 10 SAPKs and 9 ABA-inducible bZIPs using yeast-two-hybrid technique, and identified 14 positive interactions. The reliability of Y2H work was verified by in vitro pull-down assay of the key flowering regulator bZIP77 with SAPK9 and SAPK10, respectively. Moreover, SAPK10 could phosphorylate bZIP77 in vitro. Over-expression of SAPK10 resulted in earlier flowering time, at least partially through regulating the FAC-MADS15 pathway. Conclusively, our results provided an overall view of the SAPK-bZIP interactions, and shed novel lights on the mechanisms of ABA-regulated rice flowering.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Flores/fisiologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Oryza/fisiologia , Proteínas de Plantas/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Regulação da Expressão Gênica de Plantas , Fenótipo , Fosforilação , Ligação Proteica , Mapeamento de Interação de Proteínas
15.
J Agric Food Chem ; 67(15): 4214-4223, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30915847

RESUMO

Raffinose, an oligosaccharide found in many seeds, plays an important role in seed vigor; however, the regulatory mechanism governing raffinose biosynthesis remains unclear. We report here that maize W22 wild type (WT) seeds, but not W22 viviparous1 ( zmvp1) mutant seeds, start accumulating galactinol and raffinose 28 days after pollination (DAP). Transcriptome analysis of the zmvp1 embryo showed that the expression of GALACTINOL SYNTHASE2 ( GOLS2) was down-regulated relative to WT. Further experiments showed that the expression of ZmGOLS2 was up-regulated by ZmABI5 but not by ZmVP1, and it was further increased by the coexpression of ZmABI5 and ZmVP1 in maize protoplasts. ZmABI5 interacted with ZmVP1, while ZmABI5, but not ZmVP1, directly binds to the ZmGOLS2 promoter. Together, all of the findings suggest that ZmVP1 interacts with ZmABI5 and regulates ZmGOLS2 expression and raffinose accumulation in maize seeds.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Galactosiltransferases/metabolismo , Proteínas de Plantas/metabolismo , Rafinose/metabolismo , Sementes/metabolismo , Zea mays/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Galactosiltransferases/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Regiões Promotoras Genéticas , Ligação Proteica , Sementes/enzimologia , Sementes/genética , Zea mays/enzimologia , Zea mays/genética
16.
World J Gastroenterol ; 25(10): 1210-1223, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30886504

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high mortality-to-incidence ratios. Nuclear factor erythroid 2-like 3 (NFE2L3), also known as NRF3, is a member of the cap 'n' collar basic-region leucine zipper family of transcription factors. NFE2L3 is involved in the regulation of various biological processes, whereas its role in HCC has not been elucidated. AIM: To explore the expression and biological function of NFE2L3 in HCC. METHODS: We analyzed the expression of NFE2L3 in HCC tissues and its correlation with clinicopathological parameters based on The Cancer Genome Atlas (TCGA) data portal. Short hairpin RNA (shRNA) interference technology was utilized to knock down NFE2L3 in vitro. Cell apoptosis, clone formation, proliferation, migration, and invasion assays were used to identify the biological effects of NFE2L3 in BEL-7404 and SMMC-7721 cells. The expression of epithelial-mesenchymal transition (EMT) markers was examined by Western blot analysis. RESULTS: TCGA analysis showed that NFE2L3 expression was significantly positively correlated with tumor grade, T stage, and pathologic stage. The qPCR and Western blot results showed that both the mRNA and protein levels of NFE2L3 were significantly decreased after shRNA-mediated knockdown in BEL-7404 and SMMC-7721 cells. The shRNA-mediated knockdown of NFE2L3 could induce apoptosis and inhibit the clone formation and cell proliferation of SMMC-7721 and BEL-7404 cells. NFE2L3 knockdown also significantly suppressed the migration, invasion, and EMT of the two cell lines. CONCLUSION: Our study showed that shRNA-mediated knockdown of NFE2L3 exhibited tumor-suppressing effects in HCC cells.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Apoptose/genética , Fatores de Transcrição de Zíper de Leucina Básica/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Conjuntos de Dados como Assunto , Transição Epitelial-Mesenquimal/genética , Técnicas de Silenciamento de Genes , Humanos , Fígado/patologia , Neoplasias Hepáticas/patologia , Invasividade Neoplásica/genética , RNA Interferente Pequeno/metabolismo
17.
Planta ; 249(5): 1521-1533, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30712129

RESUMO

MAIN CONCLUSION: OsbZIP42 is a positive regulator of ABA signaling and drought stress tolerance. The activation of OsbZIP42 depends on stress-/ABA-activated protein kinase 4 (SAPK4) and an additional ABA-dependent modification of OsbZIP42. Basic leucine zipper transcription factors (bZIP TFs) play important roles in the ABA signaling pathway in plants. Rice OsbZIP42 is a member of the group E bZIP, which is an ortholog of Arabidopsis group A bZIP. This latter group includes abscisic acid-responsive element (ABRE)-binding factors (ABFs) involved in abiotic stress tolerance. The expression of OsbZIP42 was induced by ABA treatment, although it was not induced by drought and salt stresses. Unlike other bZIP TFs, OsbZIP42 contained two transcriptional activation domains. Although the full-length OsbZIP42 protein did not, the N-terminus of the protein interacted with SAPK4. Our results suggest that the activation of OsbZIP42 by SAPK4 requires another ABA-dependent modification of OsbZIP42. Transgenic rice overexpressing OsbZIP42 (OsbZIP42-OX) exhibited a rapidly elevated expression of the ABA-responsive LEA3 and Rab16 genes and was hypersensitive to ABA. Analyses of the OsbZIP42-OX plants revealed enhanced tolerance to drought stress. These results suggest that OsbZIP42 is a positive regulator of ABA signaling and drought stress tolerance depending on its activation, which is followed by an additional ABA-dependent modification. We propose that OsbZIP42 is an important player in rice for conferring ABA-dependent drought tolerance.


Assuntos
Ácido Abscísico/farmacologia , Oryza/efeitos dos fármacos , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Secas , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/genética , Oryza/genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/efeitos dos fármacos , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
18.
Plant Cell Rep ; 38(5): 587-596, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30712103

RESUMO

KEY MESSAGE: Overexpression of grapevine VvABF2 gene could enhance osmotic stress tolerance in Arabidopsis thaliana but fully required for ABA signaling. The abscisic acid (ABA)-dependent AREB/ABF-SnRK2 pathway has been demonstrated to play a pivotal role in response to osmotic stress in model plants. However, its function in other specific species, for example grapevine, has not been fully characterized. In this study, grapevine (Vitis vinifera L.) ABSCISIC ACID RESPONSE ELEMENT-BINDING FACTOR2 (VvABF2), a homologous gene of AREB/ABFs form Arabidopsis, was isolated and constitutively expressed in Arabidopsis under the control of the cauliflower mosaic virus 35S promoter. The VvABF2 transgenic Arabidopsis plants showed to be more sensitive to exogenous ABA compared to wild type plants and exhibited significant osmotic tolerance, like polyethylene glycol (PEG) and drought but fully required ABA for signaling. This fact was further confirmed by its downstream gene expression assays. In addition, the determination of ROS antioxidant enzymes (including SOD, POD and CAT) and the MDA of transgenic lines indicated that overexpression of VvABF2 in Arabidopsis significantly increased ROS scavenging ability and thereby reduced the cell membrane damage, which might be ABA-independent. Our results provide evidence that VvABF2 has a similar function to the Arabidopsis homolog in response to osmotic stresses, and that there is a similar ancestral function of this gene in ABA-dependent response to stresses in grapevine.


Assuntos
Ácido Abscísico/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Proteínas de Plantas/metabolismo , Vitis/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Regulação da Expressão Gênica de Plantas , Pressão Osmótica , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Vitis/genética
19.
PLoS Genet ; 15(2): e1007991, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30763307

RESUMO

Sequence-specific transcription factors (TFs) represent one of the largest groups of proteins that is targeted for SUMO post-translational modification, in both yeast and humans. SUMO modification can have diverse effects, but recent studies showed that sumoylation reduces the interaction of multiple TFs with DNA in living cells. Whether this relates to a general role for sumoylation in TF binding site selection, however, has not been fully explored because few genome-wide studies aimed at studying such a role have been reported. To address this, we used genome-wide analysis to examine how sumoylation regulates Sko1, a yeast bZIP TF with hundreds of known binding sites. We find that Sko1 is sumoylated at Lys 567 and, although many of its targets are osmoresponse genes, the level of Sko1 sumoylation is not stress-regulated and the modification does not depend or impinge on its phosphorylation by the osmostress kinase Hog1. We show that Sko1 mutants that cannot bind DNA are not sumoylated, but attaching a heterologous DNA binding domain restores the modification, implicating DNA binding as a major determinant for Sko1 sumoylation. Genome-wide chromatin immunoprecipitation (ChIP-seq) analysis shows that a sumoylation-deficient Sko1 mutant displays increased occupancy levels at its numerous binding sites, which inhibits the recruitment of the Hog1 kinase to some induced osmostress genes. This strongly supports a general role for sumoylation in reducing the association of TFs with chromatin. Extending this result, remarkably, sumoylation-deficient Sko1 binds numerous additional promoters that are not normally regulated by Sko1 but contain sequences that resemble the Sko1 binding motif. Our study points to an important role for sumoylation in modulating the interaction of a DNA-bound TF with chromatin to increase the specificity of TF-DNA interactions.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Sumoilação , Fatores de Transcrição de Zíper de Leucina Básica/química , Sítios de Ligação/genética , Imunoprecipitação da Cromatina , DNA Fúngico/genética , DNA Fúngico/metabolismo , Genes Fúngicos , Genoma Fúngico , Lisina/química , Lisina/genética , Lisina/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mutação , Pressão Osmótica , Fosforilação , Regiões Promotoras Genéticas , Proteínas Repressoras/química , Proteínas de Saccharomyces cerevisiae/química
20.
Curr Genet ; 65(3): 717-720, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30673825

RESUMO

The number of times a cell divides before irreversibly arresting is termed replicative lifespan. Despite discovery of many chemical, dietary and genetic interventions that extend replicative lifespan, usually first discovered in budding yeast and subsequently shown to apply to metazoans, there is still little understanding of the underlying molecular mechanisms involved. One unifying theme is that most, if not all, interventions that extend replicative lifespan induce "hormesis", where a little inflicted damage makes cells more able to resist similar challenges in the future. One of the many cellular changes that occur during hormesis is a global reduction in protein synthesis, which has been linked to enhanced longevity in many organisms. Our recent study in budding yeast found that it was not the reduction in protein synthesis per se, but rather the subsequent induction of the conserved Gcn4 transcriptional regulator and its ability to induce autophagy that was responsible for extending replicative lifespan. We propose that Gcn4-dependent induction of autophagy occurring downstream of reduced global protein synthesis may be a unifying molecular mechanism for many interventions that extend replicative lifespan.


Assuntos
Autofagia , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Regulação Fúngica da Expressão Gênica , Hormese , Longevidade , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética
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