scholarly journals Human E2F-1 Reactivates Cell Cycle Progression in Ventricular Myocytes and Represses Cardiac Gene Transcription

1996 ◽  
Vol 179 (2) ◽  
pp. 402-411 ◽  
Author(s):  
Lorrie A Kirshenbaum ◽  
Maha Abdellatif ◽  
Subendu Chakraborty ◽  
Michael D Schneider
Keyword(s):  
Cell Cycle ◽  
Gene Transcription ◽  
Cell Cycle Progression ◽  
Ventricular Myocytes ◽  
Cycle Progression ◽  
Cardiac Gene

scholarly journals HDAC8-dependent deacetylation of PKM2 directs nuclear localization and glycolysis to promote proliferation in hepatocellular carcinoma

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Ruixue Zhang ◽  
Mengqin Shen ◽  
Chunhua Wu ◽  
Yumei Chen ◽  
Jiani Lu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Gene Transcription ◽  
Nuclear Localization ◽  
Cell Cycle Progression ◽  
Post Translational Modification ◽  
Cycle Progression ◽  
Ccnd1 Gene ◽  
Metabolic Protein ◽  
Rate Limiting

AbstractPyruvate kinase M2 (PKM2) is not only a key rate-limiting enzyme that guides glycolysis, but also acts as a non-metabolic protein in regulating gene transcription. In recent years, a series of studies have confirmed that post-translational modification has become an important mechanism for regulating the function of PKM2, which in turn affects tumorigenesis. In this study, we found that K62 residues were deacetylated, which is related to the prognosis of HCC. Further studies indicate that HDAC8 binds and deacetylates the K62 residue of PKM2. Mechanistically, K62 deacetylation facilitate PKM2 transport into the nucleus and bind β-catenin, thereby promoting CCND1 gene transcription and cell cycle progression. In addition, the deacetylation of K62 affects the enzyme activity of PKM2 and the flux of glucose metabolism. Therefore, these results suggest that HDAC8 / PKM2 signaling may become a new target for the treatment of HCC.

scholarly journals Nuclear Myosin 1c Facilitates the Chromatin Modifications Required to Activate rRNA Gene Transcription and Cell Cycle Progression

PLoS Genetics ◽  
2013 ◽  
Vol 9 (3) ◽  
pp. e1003397 ◽  
Author(s):  
Aishe Sarshad ◽  
Fatemeh Sadeghifar ◽  
Emilie Louvet ◽  
Raffaele Mori ◽  
Stefanie Böhm ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gene Transcription ◽  
Cell Cycle Progression ◽  
Rrna Gene ◽  
Chromatin Modifications ◽  
Cycle Progression

Constitutive and Interleukin-7/Interleukin-15 Stimulated DNA Binding of Myc, Jun, and Novel Myc-Like Proteins in Cutaneous T-Cell Lymphoma Cells

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 260-267 ◽  
Author(s):  
J-Z. Qin ◽  
R. Dummer ◽  
G. Burg ◽  
U. Döbbeling
Keyword(s):  
Cell Cycle ◽  
Dna Binding ◽  
Cell Lines ◽  
Gene Transcription ◽  
Cell Cycle Progression ◽  
Cell Lymphoma ◽  
Gene Families ◽  
Cutaneous T Cell Lymphoma ◽  
Cycle Progression ◽  
Interleukin 7

Abstract Members of the Myc and Jun/Fos gene families have been found to be expressed in late stages of cutaneous T-cell lymphoma (CTCL) and may be responsible for the transition from low-grade to high-grade tumors. The composition of these complexes is an important parameter, as the different homo- and heterodimeric jun and myc complexes can have gene transcription activating or suppressing activities. We determined the composition of the jun and myc DNA-binding complexes in three CTCL cell lines and malignant cells of seven Sézary patients by electrophoretic mobility shift assays (EMSAs) and “supershift” assays in which specific antibodies against the different members of the tested gene families were included in the binding reactions. Complexes containing JunD were found in three cell lines and two patients. The three cell lines and one patient contained also c-Myc/Max heterodimers. Because c-Myc/Max heterodimers are strong gene transcription activators and are necessary for cell-cycle progression, they may play a role in the progression of CTCL. JunD may also promote cell-cycle progression and influence the expression of cell death survival genes. Interleukin-7 (IL-7) and IL-15, which have been identified as growth factors for CTCL cells, stimulated the DNA binding of JunD and two novel c-Myc recognition site (E-box) binding proteins, but not the DNA binding of c-Myc/Max heterodimers.

scholarly journals BRG1 Activates Proliferation and Transcription of Cell Cycle-Dependent Genes in Breast Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 349 ◽  
Author(s):  
Maciej Sobczak ◽  
Julita Pietrzak ◽  
Tomasz Płoszaj ◽  
Agnieszka Robaszkiewicz
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cell Lines ◽  
Gene Transcription ◽  
Breast Cancer Cells ◽  
Cell Cycle Progression ◽  
Gene Promoters ◽  
Cycle Progression ◽  
Cycle Dependent

Cancer malignancy is usually characterized by unlimited self-renewal. In some types of advanced tumors that are rapidly dividing, gene expression profiles depict elevations in pro-proliferative genes accompanied by coordinately elevated transcription of factors responsible for removal of DNA lesions. In our studies, fast proliferating breast cancer cell lines (MDA-MB-231 and MCF7), BRG1, a component of the SWI/SNF complex, emerges as an activator of functionally-linked genes responsible for activities such as mitotic cell divisions and DNA repair. Products of at least some of them are considerably overrepresented in breast cancer cells and BRG1 facilitates growth of MCF7 and MDA-MB-231 cell lines. BRG1 occurs at the promoters of genes such as CDK4, LIG1, and NEIL3, which are transcriptionally controlled by cell cycle progression and highly acetylated by EP300 in proliferating cells. As previously documented, in dividing cells BRG1 directly activates gene transcription by evicting EP300 modified nucleosomes from the promoters and, thereby, relaxing chromatin. However, the deficiency of BRG1 or EP300 activity for 48 h leads to cell growth arrest and to chromatin compaction, but also to the assembly of RB1/HDAC1/EZH2 complexes at the studied cell cycle-dependent gene promoters. Epigenetic changes include histone deacetylation and accumulation of H3K27me trimethylation, both known to repress transcription. Cell cycle arrest in G1 by inhibition of CDK4/6 phenocopies the effect of the long-term BRG1 inhibition on the chromatin structure. These results suggest that BRG1 may control gene transcription also by promoting expression of genes responsible for cell cycle progression in the studied breast cancer cells. In the current study, we show that BRG1 binding occurs at the promoters of functionally linked genes in proliferating breast cancer cells, revealing a new mechanism by which BRG1 defines gene transcription.

Constitutive and Interleukin-7/Interleukin-15 Stimulated DNA Binding of Myc, Jun, and Novel Myc-Like Proteins in Cutaneous T-Cell Lymphoma Cells

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 260-267 ◽  
Author(s):  
J-Z. Qin ◽  
R. Dummer ◽  
G. Burg ◽  
U. Döbbeling
Keyword(s):  
Cell Cycle ◽  
Dna Binding ◽  
Cell Lines ◽  
Gene Transcription ◽  
Cell Cycle Progression ◽  
Cell Lymphoma ◽  
Gene Families ◽  
Cutaneous T Cell Lymphoma ◽  
Cycle Progression ◽  
Interleukin 7

Members of the Myc and Jun/Fos gene families have been found to be expressed in late stages of cutaneous T-cell lymphoma (CTCL) and may be responsible for the transition from low-grade to high-grade tumors. The composition of these complexes is an important parameter, as the different homo- and heterodimeric jun and myc complexes can have gene transcription activating or suppressing activities. We determined the composition of the jun and myc DNA-binding complexes in three CTCL cell lines and malignant cells of seven Sézary patients by electrophoretic mobility shift assays (EMSAs) and “supershift” assays in which specific antibodies against the different members of the tested gene families were included in the binding reactions. Complexes containing JunD were found in three cell lines and two patients. The three cell lines and one patient contained also c-Myc/Max heterodimers. Because c-Myc/Max heterodimers are strong gene transcription activators and are necessary for cell-cycle progression, they may play a role in the progression of CTCL. JunD may also promote cell-cycle progression and influence the expression of cell death survival genes. Interleukin-7 (IL-7) and IL-15, which have been identified as growth factors for CTCL cells, stimulated the DNA binding of JunD and two novel c-Myc recognition site (E-box) binding proteins, but not the DNA binding of c-Myc/Max heterodimers.

scholarly journals ANKHD1 Is Required for S Phase Progression and Histone Gene Transcription in Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2002-2002
Author(s):  
Anamika Dhyani ◽  
Patricia Favro ◽  
Sara T O Saad
Keyword(s):  
Cell Cycle ◽  
Multiple Myeloma ◽  
Gene Transcription ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Histone Gene ◽  
Cycle Progression ◽  
Promoter Sequences ◽  
Core Histones ◽  
Histone Gene Transcription

Abstract Background ANKHD1, Ankyrin repeat and KH domain-containing protein 1 is highly expressed in CD138+ cells of patients with multiple myeloma (MM) as well as in MM cell lines (U266, RPMI 8226 ,MM1S and MM1R. Our microarray studies showed modulation of several histone variants after ANKHD1 silencing (not published). Furthermore ANKHD1 silencing in MM cell lines resulted in S phase arrest (1). As genes involved in histone transcription are upregulated in S phase, and ANKHD1 downregulation inhibits cell cycle progression at S phase, we hypothesized that ANKHD1 might be a protein that gets upregulated in S phase and plays a role in histone gene transcription. Hence, in the present study ANKHD1 expression was sought at different phases of cell cycle and a possible interaction of ANKHD1 with histones was also investigated, in addition to the effect of ANKHD1 downregulation on histone expression in a MM cell line. Methods MM cell line U266 was synchronized at G1 phase by serum starvation (16h), S phase by double thymidine block (2mM) followed by release in 24 μM deoxycytidine (4h) or G2 phase by nocodazole treatment(50ng/ml;16h). Cells were stained with PI and analyzed by flow cytometry for DNA content. Percentage of cells in G1, S, or G2/M was calculated using the ModFit program. Western blot was then carried out for ANKHD1 expression in U266 cells untreated or synchronized at different G1, S and G2 phases of cell cycle. ANKHD1 expression was inhibited by lentiviral mediated ANKHD1shRNA transduction and its effect on expression of histones was studied by qPCR and immunoblot. Further chromatin immunoprecipitation (ChIP) assay was performed to study the interaction between ANKHD1 and histones using EZ-Magna ChIP™ A kit(Millipore) followed by qPCR with primers specific to core histones promoter region. Immunofluorescence was performed to determine the localization of ANKHD1 before and after leptomycin B treatment of U266 cells. Results. In the present study, endogenous ANKHD1 expression showed a clear cell-cycle-dependence, peaking during S phase, when cells were synchronized by double thymidine block followed by deoxycytidine release. Further down-regulation of ANKHD1 expression in U266 cells by lentiviral mediated shRNA against ANKHD1 resulted in a significant reduction of histones (p<0.05) at both mRNA and protein levels. Chromatin immunoprecipitation followed by qPCR with primers specific to core histones promoter region showed that ANKHD1, though not IgG (negative control) coprecipitated with histone gene chromatin, thus confirming the interaction between the core histone promoter regions and ANKHD1. Fold enrichment (mean ± sd) of promoter sequences bound to ANKHD1 were 7.74 ± 0.048, 7.78± 0.129 and 7.06± 0.178 for histones H2B/r, H3/c and H4/e, respectively. Immunofluorescence after leptomycin B treatment (20ng/ml) of U266 wild type cells for 24 hours showed accumulation of ANKHD1 inside nucleus as compared to untreated cells where ANKHD1 was found to be predominantly in cytoplasm. This suggests transport of ANKHD1 between nucleus and cytoplasm. Conclusion ANKHD1 expression peaks during S phase of cell cycle and downregulation of ANKHD1 protein by shRNA results in downregulation of histones. ANKHD1 interacts with histone gene promoter sequences and modulates histones transcription. These results suggest that ANKHD1 might be an important component of the machinery required for histone mRNA expression and cell-cycle progression. Furthermore, ANKHD1 protein which was earlier reported to be localized predominantly in cytoplasm (1) is herein suggested to shuttle between cytoplasm and nucleus thereby playing a role in gene regulation. Extensive studies are required to understand the mechanism underlying the regulation of gene transcription by ANKHD1. References: 1) ANKHD1 regulates cell cycle progression and proliferation in multiple myeloma cells. Dhyani et al. FEBS letters 2012. Disclosures No relevant conflicts of interest to declare.

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