scholarly journals CHOP Enhancement of Gene Transcription by Interactions with Jun/Fos AP-1 Complex Proteins

1999 ◽  
Vol 19 (11) ◽  
pp. 7589-7599 ◽  
Author(s):  
Mariano Ubeda ◽  
Mario Vallejo ◽  
Joel F. Habener
Keyword(s):  
Transcription Factor ◽  
Gene Transcription ◽  
Stress Responses ◽  
Leucine Zipper ◽  
Target Genes ◽  
Cellular Stress ◽  
Dominant Negative ◽  
Dimerization Domain ◽  
Mobility Shift

ABSTRACT The transcription factor CHOP (C/EBP homologous protein 10) is a bZIP protein induced by a variety of stimuli that evoke cellular stress responses and has been shown to arrest cell growth and to promote programmed cell death. CHOP cannot form homodimers but forms stable heterodimers with the C/EBP family of activating transcription factors. Although initially characterized as a dominant negative inhibitor of C/EBPs in the activation of gene transcription, CHOP-C/EBP can activate certain target genes. Here we show that CHOP interacts with members of the immediate-early response, growth-promoting AP-1 transcription factor family, JunD, c-Jun, and c-Fos, to activate promoter elements in the somatostatin, JunD, and collagenase genes. The leucine zipper dimerization domain is required for interactions with AP-1 proteins and transactivation of transcription. Analyses by electrophoretic mobility shift assays and by an in vivo mammalian two-hybrid system for protein-protein interactions indicate that CHOP interacts with AP-1 proteins inside cells and suggest that it is recruited to the AP-1 complex by a tethering mechanism rather than by direct binding of DNA. Thus, CHOP not only is a negative or a positive regulator of C/EBP target genes but also, when tethered to AP-1 factors, can activate AP-1 target genes. These findings establish the existence of a new mechanism by which CHOP regulates gene expression when cells are exposed to cellular stress.

scholarly journals Identification of human myometrial target genes of the c-Jun NH2-terminal kinase (JNK) pathway: the role of activating transcription factor 2 (ATF2) and a novel spliced isoform ATF2-small

2005 ◽  
Vol 34 (1) ◽  
pp. 19-35 ◽  
Author(s):  
Jarrod Bailey ◽  
G Nicholas Europe-Finner
Keyword(s):  
Transcription Factor ◽  
Stress Responses ◽  
Leucine Zipper ◽  
Target Genes ◽  
Mitogen Activated Protein Kinase ◽  
Human Myometrium ◽  
Suppression Subtractive Hybridisation ◽  
Jnk Pathway ◽  
Activating Transcription Factor

Activating transcription factor 2 (ATF2), a ubiquitously expressed member of the basic region leucine zipper (bZIP) family of transcription factors activated by mitogen activated protein kinase (MAPK) pathways, is important in the mediation of cellular stress responses, development and transformation. We have previously reported the differential expression of active ATF2 in the human myometrium throughout pregnancy and labour, and identified and partially characterized a novel splice variant ATF2-small (ATF2-sm). To further understand the role of these factors in the myometrium, we have used gene microarrays to define the target genes in cultured myometrial cells stably-transfected with ATF2 and ATF2-sm cDNAs. Many of the genes identified appear to have potential roles in regulating myometrial function and include proteins involved in G-protein receptor signalling, cytokine signalling, transcriptional regulation, cell-cycle control, formation of the extracellular matrix and cytoskeletal architecture. ATF2 was found to affect the expression of 204 genes; 113 being up-regulated and 91 down-regulated whereas the novel ATF2-sm factor altered the expression of 55 genes; expression was increased in 29 cases and decreased in 26. A further 25 genes affected by ATF2-sm were identified by suppression subtractive hybridisation (SSH). Notably, the genes affected by ATF2 and ATF2-sm appear to belong to discrete groups: only two genes were affected by both factors.

scholarly journals Overexpressing the HD-Zip class II transcription factor EcHB1 from Eucalyptus camaldulensis increased the leaf photosynthesis and drought tolerance of Eucalyptus

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Keisuke Sasaki ◽  
Yuuki Ida ◽  
Sakihito Kitajima ◽  
Tetsu Kawazu ◽  
Takashi Hibino ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Leaf Area ◽  
Leucine Zipper ◽  
Eucalyptus Grandis ◽  
Eucalyptus Camaldulensis ◽  
Class Ii ◽  
Cell Multiplication ◽  
Leaf Photosynthesis ◽  
Unit Leaf

Abstract Alteration in the leaf mesophyll anatomy by genetic modification is potentially a promising tool for improving the physiological functions of trees by improving leaf photosynthesis. Homeodomain leucine zipper (HD-Zip) transcription factors are candidates for anatomical alterations of leaves through modification of cell multiplication, differentiation, and expansion. Full-length cDNA encoding a Eucalyptus camaldulensis HD-Zip class II transcription factor (EcHB1) was over-expressed in vivo in the hybrid Eucalyptus GUT5 generated from Eucalyptus grandis and Eucalyptus urophylla. Overexpression of EcHB1 induced significant modification in the mesophyll anatomy of Eucalyptus with enhancements in the number of cells and chloroplasts on a leaf-area basis. The leaf-area-based photosynthesis of Eucalyptus was improved in the EcHB1-overexpression lines, which was due to both enhanced CO2 diffusion into chloroplasts and increased photosynthetic biochemical functions through increased number of chloroplasts per unit leaf area. Additionally, overexpression of EcHB1 suppressed defoliation and thus improved the growth of Eucalyptus trees under drought stress, which was a result of reduced water loss from trees due to the reduction in leaf area with no changes in stomatal morphology. These results gave us new insights into the role of the HD-Zip II gene.

scholarly journals Identification of target genes and a unique cis element regulated by IRF-8 in developing macrophages

Blood ◽  
2005 ◽  
Vol 106 (6) ◽  
pp. 1938-1947 ◽  
Author(s):  
Tomohiko Tamura ◽  
Pratima Thotakura ◽  
Tetsuya S. Tanaka ◽  
Minoru S. H. Ko ◽  
Keiko Ozato
Keyword(s):  
Transcription Factor ◽  
Cystatin C ◽  
Target Genes ◽  
De Novo ◽  
Consensus Sequence ◽  
Binding Motif ◽  
Microarray Gene Expression ◽  
Cathepsin C ◽  
Cis Element

Abstract Interferon regulatory factor-8 (IRF-8)/interferon consensus sequence–binding protein (ICSBP) is a transcription factor that controls myeloid-cell development. Microarray gene expression analysis of Irf-8-/- myeloid progenitor cells expressing an IRF-8/estrogen receptor chimera (which differentiate into macrophages after addition of estradiol) was used to identify 69 genes altered by IRF-8 during early differentiation (62 up-regulated and 7 down-regulated). Among them, 4 lysosomal/endosomal enzyme-related genes (cystatin C, cathepsin C, lysozyme, and prosaposin) did not require de novo protein synthesis for induction, suggesting that they were direct targets of IRF-8. We developed a reporter assay system employing a self-inactivating retrovirus and analyzed the cystatin C and cathepsin C promoters. We found that a unique cis element mediates IRF-8–induced activation of both promoters. Similar elements were also found in other IRF-8 target genes with a consensus sequence (GAAANN[N]GGAA) comprising a core IRF-binding motif and an Ets-binding motif; this sequence is similar but distinct from the previously reported Ets/IRF composite element. Chromatin immunoprecipitation assays demonstrated that IRF-8 and the PU.1 Ets transcription factor bind to this element in vivo. Collectively, these data indicate that IRF-8 stimulates transcription of target genes through a novel cis element to specify macrophage differentiation.

scholarly journals Regulation of Nitrate (NO3) Transporters and Glutamate Synthase-Encoding Genes under Drought Stress in Arabidopsis: The Regulatory Role of AtbZIP62 Transcription Factor

Plants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2149
Author(s):  
Nkulu Kabange Rolly ◽  
Byung-Wook Yun
Keyword(s):  
Transcription Factor ◽  
Drought Stress ◽  
Leucine Zipper ◽  
Target Genes ◽  
De Novo ◽  
In Silico Analysis ◽  
Glutamate Synthase ◽  
Regulatory Elements ◽  
Transcript Accumulation ◽  
Basic Leucine Zipper

Nitrogen (N) is an essential macronutrient, which contributes substantially to the growth and development of plants. In the soil, nitrate (NO3) is the predominant form of N available to the plant and its acquisition by the plant involves several NO3 transporters; however, the mechanism underlying their involvement in the adaptive response under abiotic stress is poorly understood. Initially, we performed an in silico analysis to identify potential binding sites for the basic leucine zipper 62 transcription factor (AtbZIP62 TF) in the promoter of the target genes, and constructed their protein–protein interaction networks. Rather than AtbZIP62, results revealed the presence of cis-regulatory elements specific to two other bZIP TFs, AtbZIP18 and 69. A recent report showed that AtbZIP62 TF negatively regulated AtbZIP18 and AtbZIP69. Therefore, we investigated the transcriptional regulation of AtNPF6.2/NRT1.4 (low-affinity NO3 transporter), AtNPF6.3/NRT1.1 (dual-affinity NO3 transporter), AtNRT2.1 and AtNRT2.2 (high-affinity NO3 transporters), and AtGLU1 and AtGLU2 (both encoding glutamate synthase) in response to drought stress in Col-0. From the perspective of exploring the transcriptional interplay of the target genes with AtbZIP62 TF, we measured their expression by qPCR in the atbzip62 (lacking the AtbZIP62 gene) under the same conditions. Our recent study revealed that AtbZIP62 TF positively regulates the expression of AtPYD1 (Pyrimidine 1, a key gene of the de novo pyrimidine biosynthesis pathway know to share a common substrate with the N metabolic pathway). For this reason, we included the atpyd1-2 mutant in the study. Our findings revealed that the expression of AtNPF6.2/NRT1.4, AtNPF6.3/NRT1.1 and AtNRT2.2 was similarly regulated in atzbip62 and atpyd1-2 but differentially regulated between the mutant lines and Col-0. Meanwhile, the expression pattern of AtNRT2.1 in atbzip62 was similar to that observed in Col-0 but was suppressed in atpyd1-2. The breakthrough is that AtNRT2.2 had the highest expression level in Col-0, while being suppressed in atbzip62 and atpyd1-2. Furthermore, the transcript accumulation of AtGLU1 and AtGLU2 showed differential regulation patterns between Col-0 and atbzip62, and atpyd1-2. Therefore, results suggest that of all tested NO3 transporters, AtNRT2.2 is thought to play a preponderant role in contributing to NO3 transport events under the regulatory influence of AtbZIP62 TF in response to drought stress.

Protein signaling and regulation of gene transcription in leukemia: role of the Casein Kinase II-Ikaros axis

2016 ◽  
Vol 64 (3) ◽  
pp. 735-739 ◽  
Author(s):  
Chandrika S Gowda ◽  
Chunhua Song ◽  
Yali Ding ◽  
Malika Kapadia ◽  
Sinisa Dovat
Keyword(s):  
Gene Transcription ◽  
Target Genes ◽  
Cellular Proliferation ◽  
Lymphoblastic Leukemia ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
Casein Kinase Ii ◽  
Casein Kinase ◽  
Protein Signaling

Protein signaling and regulation of gene expression are the two major mechanisms that regulate cellular proliferation in leukemia. Discerning the function of these processes is essential for understanding the pathogenesis of leukemia and for developing the targeted therapies. Here, we provide an overview of one of the mechanisms that regulates gene transcription in leukemia. This mechanism involves the direct interaction between Casein Kinase II (CK2) and the Ikaros transcription factor. Ikaros (IKZF1) functions as a master regulator of hematopoiesis and a tumor suppressor in acute lymphoblastic leukemia (ALL). Impaired Ikaros function results in the development of high-risk leukemia. Ikaros binds to the upstream regulatory elements of its target genes and regulates their transcription via chromatin remodeling. In vivo, Ikaros is a target for CK2, a pro-oncogenic kinase. CK2 directly phosphorylates Ikaros at multiple amino acids. Functional experiments showed that CK2-mediated phosphorylation of Ikaros, regulates Ikaros’ DNA binding affinity, subcellular localization and protein stability. Recent studies revealed that phosphorylation of Ikaros by CK2 regulates Ikaros binding and repression of the terminal deoxytransferase (TdT) gene in normal thymocytes and in T-cell ALL. Available data suggest that the oncogenic activity of CK2 in leukemia involves functional inactivation of Ikaros and provide a rationale for CK2 inhibitors as a potential treatment for ALL.

Regulation of Hox target genes by a DNA bound Homothorax/Hox/Extradenticle complex

Development ◽  
1999 ◽  
Vol 126 (22) ◽  
pp. 5137-5148 ◽  
Author(s):  
H.D. Ryoo ◽  
T. Marty ◽  
F. Casares ◽  
M. Affolter ◽  
R.S. Mann
Keyword(s):  
Nuclear Localization ◽  
Target Genes ◽  
Dominant Negative ◽  
Homeodomain Protein ◽  
Hox Proteins ◽  
Trimeric Complex ◽  
Binding Residue ◽  
Dominant Negative Form

To regulate their target genes, the Hox proteins of Drosophila often bind to DNA as heterodimers with the homeodomain protein Extradenticle (EXD). For EXD to bind DNA, it must be in the nucleus, and its nuclear localization requires a third homeodomain protein, Homothorax (HTH). Here we show that a conserved N-terminal domain of HTH directly binds to EXD in vitro, and is sufficient to induce the nuclear localization of EXD in vivo. However, mutating a key DNA binding residue in the HTH homeodomain abolishes many of its in vivo functions. HTH binds to DNA as part of a HTH/Hox/EXD trimeric complex, and we show that this complex is essential for the activation of a natural Hox target enhancer. Using a dominant negative form of HTH we provide evidence that similar complexes are important for several Hox- and exd-mediated functions in vivo. These data suggest that Hox proteins often function as part of a multiprotein complex, composed of HTH, Hox, and EXD proteins, bound to DNA.

scholarly journals Strigolactone GR24 upregulates Nrf2 target genes and may protect against oxidative stress in skeletal muscle

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1459
Author(s):  
Shalem Raju Modi ◽  
Tarja Kokkola
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Skeletal Muscle ◽  
Transcription Factor ◽  
Stress Responses ◽  
Mycorrhizal Fungi ◽  
Target Genes ◽  
Redox Homeostasis ◽  
Antioxidant Defences ◽  
Microarray Gene Expression

GR24 is a synthetic strigolactone analog, demonstrated to regulate the development of plants and arbuscular mycorrhizal fungi. GR24 possesses anti-cancer and anti-apoptotic properties, enhances insulin sensitivity and mitochondrial biogenesis in skeletal myotubes, inhibits adipogenesis, decreases inflammation in adipocytes and macrophages and downregulates the expression of hepatic gluconeogenic enzymes. Transcription factor Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) is a master regulator of antioxidant response, regulating a multitude of genes involved in cellular stress responses and anti-inflammatory pathways, thus maintaining cellular redox homeostasis. Nrf2 activation reduces the deleterious effects of mitochondrial toxins and has multiple roles in promoting mitochondrial function and dynamics. We studied the role of GR24 on gene expression in rat L6 skeletal muscle cells which were differentiated into myotubes. The myotubes were treated with GR24 and analyzed by microarray gene expression profiling. GR24 upregulated the cytoprotective transcription factor Nrf2 and its target genes, activating antioxidant defences, suggesting that GR24 may protect skeletal muscle from the toxic effects of oxidative stress.

scholarly journals Leukemia-Related Transcription Factor TEL Is Negatively Regulated through Extracellular Signal-Regulated Kinase-Induced Phosphorylation

2004 ◽  
Vol 24 (8) ◽  
pp. 3227-3237 ◽  
Author(s):  
Kazuhiro Maki ◽  
Honoka Arai ◽  
Kazuo Waga ◽  
Ko Sasaki ◽  
Fumihiko Nakamura ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Dominant Negative ◽  
Mitogen Activated Protein Kinase ◽  
Dominant Negative Effect ◽  
Phosphorylation Sites ◽  
3T3 Cells ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ABSTRACT TEL is an ETS family transcription factor that possesses multiple putative mitogen-activated protein kinase phosphorylation sites. We here describe the functional regulation of TEL via ERK pathways. Overexpressed TEL becomes phosphorylated in vivo by activated ERK. TEL is also directly phosphorylated in vitro by ERK. The inducible phosphorylation sites are Ser213 and Ser257. TEL binds to a common docking domain in ERK. In vivo ERK-dependent phosphorylation reduces trans-repressional and DNA-binding abilities of TEL for ETS-binding sites. A mutant carrying substituted glutamates on both Ser213 and Ser257 functionally mimics hyperphosphorylated TEL and also shows a dominant-negative effect on TEL-induced transcriptional suppression. Losing DNA-binding affinity through phosphorylation but heterodimerizing with unmodified TEL could be an underlying mechanism. Moreover, the glutamate mutant dominantly interferes with TEL-induced erythroid differentiation in MEL cells and growth suppression in NIH 3T3 cells. Finally, endogenous TEL is dephosphorylated in parallel with ERK inactivation in differentiating MEL cells and is phosphorylated through ERK activation in Ras-transformed NIH 3T3 cells. These data indicate that TEL is a constituent downstream of ERK in signal transduction systems and is physiologically regulated by ERK in molecular and biological features.

Activating transcription factor 2 increases transactivation and protein stability of hypoxia-inducible factor 1α in hepatocytes

2009 ◽  
Vol 424 (2) ◽  
pp. 285-296 ◽  
Author(s):  
Jeong Hae Choi ◽  
Hyun Kook Cho ◽  
Yung Hyun Choi ◽  
JaeHun Cheong
Keyword(s):  
Transcription Factor ◽  
Protein Stability ◽  
Gene Transcription ◽  
Hypoxia Inducible Factor ◽  
Protein Stabilization ◽  
Hypoxic Conditions ◽  
Tumour Suppressor Protein ◽  
Activating Transcription Factor

HIF-1 (hypoxia inducible factor 1) performs a crucial role in mediating the response to hypoxia. However, other transcription factors are also capable of regulating hypoxia-induced target-gene transcription. In a previous report, we demonstrated that the transcription factor ATF-2 (activating transcription factor 2) regulates hypoxia-induced gene transcription, along with HIF-1α. In the present study, we show that the protein stability of ATF-2 is induced by hypoxia and the hypoxia-mimic CoCl2 (cobalt chloride), and that ATF-2 induction enhances HIF-1α protein stability via direct protein interaction. The knockdown of ATF-2 using small interfering RNA and translation-inhibition experiments demonstrated that ATF-2 plays a key role in the maintenance of the expression level and transcriptional activity of HIF-1α. Furthermore, we determined that ATF-2 interacts directly with HIF-1α both in vivo and in vitro and competes with the tumour suppressor protein p53 for HIF-1α binding. Collectively, these results show that protein stabilization of ATF-2 under hypoxic conditions is required for the induction of the protein stability and transactivation activity of HIF-1α for efficient hypoxia-associated gene expression.

scholarly journals Physical and Functional Interactions between Homeodomain NKX2.1 and Winged Helix/Forkhead FOXA1 in Lung Epithelial Cells

2007 ◽  
Vol 27 (6) ◽  
pp. 2155-2165 ◽  
Author(s):  
Parviz Minoo ◽  
Lingyan Hu ◽  
Yiming Xing ◽  
Nian Ling Zhu ◽  
Hongyan Chen ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Epithelial Cells ◽  
Target Genes ◽  
Lung Epithelial Cells ◽  
Mobility Shift ◽  
Independent Manner ◽  
Winged Helix ◽  
Gradient Distribution ◽  
Functional Interactions

ABSTRACT NKX2.1 is a homeodomain transcription factor that controls development of the brain, lung, and thyroid. In the lung, Nkx2.1 is expressed in a proximo-distal gradient and activates specific genes in phenotypically distinct epithelial cells located along this axis. The mechanisms by which NKX2.1 controls its target genes may involve interactions with other transcription factors. We examined whether NKX2.1 interacts with members of the winged-helix/forkhead family of FOXA transcription factors to regulate two spatially and cell type-specific genes, SpC and Ccsp. The results show that NKX2.1 interacts physically and functionally with FOXA1. The nature of the interaction is inhibitory and occurs through the NKX2.1 homeodomain in a DNA-independent manner. On SpC, which lacks a FOXA1 binding site, FOXA1 attenuates NKX2.1-dependent transcription. Inhibition of FOXA1 by small interfering RNA increased SpC mRNA, demonstrating the in vivo relevance of this finding. In contrast, FOXA1 and NKX2.1 additively activate transcription from Ccsp, which includes both NKX2.1 and FOXA1 binding sites. In electrophoretic mobility shift assays, the GST-FOXA1 fusion protein interferes with the formation of NKX2.1 transcriptional complexes by potentially masking the latter's homeodomain DNA binding function. These findings suggest a novel mode of selective gene regulation by proximo-distal gradient distribution of and functional interactions between forkhead and homeodomain transcription factors.

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