Nuclear translocation of the heterotrimeric CCAAT binding factor of Aspergillus oryzae is dependent on two redundant localising signals in a single subunit

2005 ◽  
Vol 184 (2) ◽  
pp. 93-100 ◽  
Author(s):  
Hideya Goda ◽  
Takashi Nagase ◽  
Shinjiro Tanoue ◽  
Junya Sugiyama ◽  
Stefan Steidl ◽  
...  
Keyword(s):  
Aspergillus Oryzae ◽  
Nuclear Translocation ◽  
Binding Factor ◽  
Single Subunit

scholarly journals Cytoplasmic Sequestration of the Polyomavirus Enhancer Binding Protein 2 (PEBP2)/Core Binding Factor α (CBFα) Subunit by the Leukemia-Related PEBP2/CBFβ-SMMHC Fusion Protein Inhibits PEBP2/CBF-Mediated Transactivation

1998 ◽  
Vol 18 (7) ◽  
pp. 4252-4261 ◽  
Author(s):  
Yuka Kanno ◽  
Tomohiko Kanno ◽  
Chohei Sakakura ◽  
Suk-Chul Bae ◽  
Yoshiaki Ito
Keyword(s):  
Nuclear Translocation ◽  
Binding Protein ◽  
Myelogenous Leukemia ◽  
Luciferase Assay ◽  
Β Subunit ◽  
Core Binding Factor ◽  
Α Subunit ◽  
Enhancer Binding Protein ◽  
Binding Factor ◽  
Minimal Region

ABSTRACT The polyomavirus enhancer binding protein 2 (PEBP2)/core binding factor (CBF) is a transcription factor composed of two subunits, α and β. The gene encoding the β subunit is disrupted by inv(16), resulting in the formation of a chimeric protein, β-SMMHC, which is associated with acute myelogenous leukemia. To understand the effect of β-SMMHC on PEBP2-mediated transactivation, we used a luciferase assay system in which contribution of both the α and β subunits was absolutely required to activate transcription. Using this system, we found that the minimal region of the β subunit required for transactivation resides between amino acid 1 and 135, which is known to dimerize with the α subunit. In contrast, β-SMMHC, despite having this minimal region for dimerization and transactivation, failed to support transcription with the α subunit. Furthermore β-SMMHC blocked the synergistic transcription achieved by PEBP2 and CCAAT/enhancer binding protein α. By using a construct in which the PEBP2 α subunit was fused to the glucocorticoid receptor ligand binding domain, we demonstrated that coexpressed β-SMMHC tightly sequestered the α subunit in the cytoplasm and blocked dexamethasone-dependent nuclear translocation of the α subunit. Thus, the result suggess that β-SMMHC inhibits PEBP2-mediated transcription via cytoplasmic sequestration of the α subunit. Lastly proliferation of ME-1 cells that harbor inv(16) was blocked by an antisense oligonucleotide complementary to the junction of the chimeric mRNA, suggesting that β-SMMHC contributes to leukemogenesis by blocking the differentiation of myeloid cells.

Autophagy deficiency boosts the production of kojic acid in the filamentous fungus Aspergillus oryzae

2021 ◽  
Author(s):  
Junlin Chen ◽  
Manabu Arioka
Keyword(s):  
Transcription Factor ◽  
Aspergillus Oryzae ◽  
Filamentous Fungus ◽  
Nuclear Translocation ◽  
Kojic Acid ◽  
Expression Of Genes

Abstract We found that the expression of genes involved in kojic acid (KA) biosynthesis, kojA, kojR, and kojT, was highly elevated in the Aspergillus oryzae autophagy-deficient mutants. In agreement, KA production was much increased in these mutants. Nuclear translocation of KojR, a transcription factor, was observed in the autophagy mutants before they were starved, explaining why KA production was boosted.

scholarly journals Novel Transcription Factor-Like Function of Human Matrix Metalloproteinase 3 Regulating the CTGF/CCN2 Gene

2008 ◽  
Vol 28 (7) ◽  
pp. 2391-2413 ◽  
Author(s):  
Takanori Eguchi ◽  
Satoshi Kubota ◽  
Kazumi Kawata ◽  
Yoshiki Mukudai ◽  
Junji Uehara ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Nuclear Translocation ◽  
Tissue Growth ◽  
Nuclear Localization Signals ◽  
Matrix Metalloproteinase 3 ◽  
Osteoarthritic Chondrocytes ◽  
Binding Factor ◽  
Gel Shift Assay ◽  
Mutant Promoter

ABSTRACT Matrix metalloproteinase 3 (MMP3) is well known as a secretory endopeptidase that degrades extracellular matrices. Recent reports indicated the presence of MMPs in the nucleus (A. J. Kwon et al., FASEB J. 18:690-692, 2004); however, its function has not been well investigated. Here, we report a novel function of human nuclear MMP3 as a trans regulator of connective tissue growth factor (CCN2/CTGF). Initially, we cloned MMP3 cDNA as a DNA-binding factor for the CCN2/CTGF gene. An interaction between MMP3 and transcription enhancer dominant in chondrocytes (TRENDIC) in the CCN2/CTGF promoter was confirmed by a gel shift assay and chromatin immunoprecipitation. The CCN2/CTGF promoter was activated by overexpressed MMP3, whereas a TRENDIC mutant promoter lost the response. Also, the knocking down of MMP3 suppressed CCN2/CTGF expression. By cytochemical and histochemical analyses, MMP3 was detected in the nuclei of chondrocytic cells in culture and also in the nuclei of normal and osteoarthritic chondrocytes in vivo. The nuclear translocation of externally added recombinant MMP3 and six putative nuclear localization signals in MMP3 also were shown. Furthermore, we determined that heterochromatin protein gamma coordinately regulates CCN2/CTGF by interacting with MMP3. The involvement of this novel role of MMP3 in the development, tissue remodeling, and pathology of arthritic diseases through CCN2/CTGF regulation thus is suggested.

Insulin-Like Growth Factor I Receptor Signaling and Nuclear Translocation of Insulin Receptor Substrates 1 and 2

2003 ◽  
Vol 17 (3) ◽  
pp. 472-486 ◽  
Author(s):  
HongZhi Sun ◽  
Xiao Tu ◽  
Marco Prisco ◽  
An Wu ◽  
Ivan Casiburi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Insulin Receptor ◽  
Ribosomal Dna ◽  
Nuclear Translocation ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Binding Factor ◽  
Irs Proteins ◽  
Upstream Binding Factor

Abstract The insulin receptor substrate 1 (IRS-1) can translocate to the nuclei and nucleoli of several types of cells. Nuclear translocation can be induced by an activated insulin-like growth factor 1 receptor (IGF-IR), and by certain oncogenes, such as the Simian virus 40 T antigen and v-src. We have asked whether IRS-2 could also translocate to the nuclei. In addition, we have studied the effects of functional mutations in the IGF-IR on nuclear translocation of IRS proteins. IRS-2 translocates to the nuclei of mouse embryo fibroblasts expressing the IGF-IR, but, at variance with IRS-1, does not translocate in cells expressing the Simian virus 40 T antigen. Mutations in the tyrosine kinase domain of the IGF-IR abrogate translocation of the IRS proteins. Other mutations in the IGF-IR, which do not interfere with its mitogenicity but inhibit its transforming capacity, result in a decrease in translocation, especially to the nucleoli. Nuclear IRS-1 and IRS-2 interact with the upstream binding factor, which is a key regulator of RNA polymerase I activity and, therefore, rRNA synthesis. In 32D cells, wild-type, but not mutant, IRS-1 causes a significant activation of the ribosomal DNA promoter. The interaction of nuclear IRS proteins with upstream binding factor 1 constitutes the first direct link of these proteins with the ribosomal DNA transcription machinery.

scholarly journals Cellular senescence promotes endothelial activation through epigenetic alteration, and consequently accelerates atherosclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sakiko Honda ◽  
Koji Ikeda ◽  
Ryota Urata ◽  
Ekura Yamazaki ◽  
Noriaki Emoto ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Atherosclerotic Lesion ◽  
Endothelial Activation ◽  
Dominant Negative ◽  
Epigenetic Alteration ◽  
Dominant Negative Form ◽  
Promising Therapeutic Target ◽  
Binding Factor

AbstractSenescent vascular cells are detected in atherosclerotic lesion, and its involvement in the development of atherosclerosis has been revealed; however, whether and the mechanism by which endothelial cell (EC) senescence is causally implicated in atherosclerosis remains unclear. We here investigate a role of EC senescence in atherosclerosis by utilizing EC-specific progeroid mice that overexpress the dominant negative form of telomeric repeat-binding factor 2 under the control of the Tie2 or vascular endothelial cadherin promoter. EC-specific progeria accelerated atherosclerosis in mice with target deletion of ApoE. Mechanistically, senescent ECs were markedly sensitive for inflammation-mediated VCAM-1 induction, leading to enhanced monocyte adhesion. Inhibition of NF-κB signaling abolished the enhanced inflammatory responses in senescent ECs, while NF-κB nuclear translocation in response to TNF-α were similar between young and senescent ECs. We found a higher association of VCAM-1 gene with active histone H3 trimethylated on lysine 4, leading to increased NF-κB accessibility in senescent ECs. Our data revealed that EC cellular senescence causes endothelial hyper-inflammability through epigenetic alteration, which consequently accelerates atherosclerosis. Therefore, EC senescence is a promising therapeutic target for the prevention and/or treatment of atherosclerotic disease in elderly population.

A role for upstream binding factor in organizing ribosomal gene chromatin

2006 ◽  
Vol 73 ◽  
pp. 77-84 ◽  
Author(s):  
Jane E. Wright ◽  
Christine Mais ◽  
José-Luis Prieto ◽  
Brian McStay
Keyword(s):  
Nucleolar Organizer ◽  
Ribosomal Gene ◽  
Rna Polymerase I ◽  
Nucleolar Organizer Regions ◽  
Binding Factor ◽  
Upstream Binding Factor ◽  
Acrocentric Chromosomes ◽  
Polymerase I ◽  
Secondary Constrictions ◽  
Active Nors

Human ribosomal genes are located in NORs (nucleolar organizer regions) on the short arms of acrocentric chromosomes. During metaphase, previously active NORs appear as prominent chromosomal features termed secondary constrictions, which are achromatic in chromosome banding and positive in silver staining. The architectural RNA polymerase I transcription factor UBF (upstream binding factor) binds extensively across the ribosomal gene repeat throughout the cell cycle. Evidence that UBF underpins NOR structure is provided by an examination of cell lines in which large arrays of a heterologous UBF binding sequences are integrated at ectopic sites on human chromosomes. These arrays efficiently recruit UBF even to sites outside the nucleolus, and during metaphase form novel silver-stainable secondary constrictions, termed pseudo-NORs, that are morphologically similar to NORs.

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