scholarly journals Cdc14b regulates mammalian RNA polymerase II and represses cell cycle transcription

2011 ◽  
Vol 1 (1) ◽  
Author(s):  
María Guillamot ◽  
Eusebio Manchado ◽  
Massimo Chiesa ◽  
Gonzalo Gómez-López ◽  
David G. Pisano ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Rna Polymerase ◽  
Rna Polymerase Ii

scholarly journals Cell cycle-dependent regulation of RNA polymerase II basal transcription activity

1995 ◽  
Vol 23 (20) ◽  
pp. 4050-4054 ◽  
Author(s):  
Masatomo Yonaha ◽  
Taku Chibazakura ◽  
Shigetaka Kitajima ◽  
Yukio Yasukochi
Keyword(s):  
Cell Cycle ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Basal Transcription ◽  
Transcription Activity ◽  
Cycle Dependent

scholarly journals Joint changes in RNA, RNA polymerase II, and promoter activity through the cell cycle identify non-coding RNAs involved in proliferation

2021 ◽  
Author(s):  
Siv Anita Hegre ◽  
Helle Samdal ◽  
Antonin Klima ◽  
Endre B. Stovner ◽  
Kristin G. Nørsett ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Promoter Activity ◽  
Cycle Phase ◽  
Specific Expression ◽  
Chip Sequencing ◽  
Non Coding Rnas ◽  
Cycle Dependent ◽  
Rna Levels

AbstractProper regulation of the cell cycle is necessary for normal growth and development of all organisms. Conversely, altered cell cycle regulation often underlies proliferative diseases such as cancer. Long non-coding RNAs (lncRNAs) are recognized as important regulators of gene expression and are often found dysregulated in diseases, including cancers. However, identifying lncRNAs with cell cycle functions is challenging due to their often low and cell-type specific expression. We present a highly effective method that analyses changes in promoter activity, transcription, and RNA levels for identifying genes enriched for cell cycle functions. Specifically, by combining RNA sequencing with ChIP sequencing through the cell cycle of synchronized human keratinocytes, we identified 1009 genes with cell cycle-dependent expression and correlated changes in RNA polymerase II occupancy or promoter activity as measured by histone 3 lysine 4 trimethylation (H3K4me3). These genes were highly enriched for genes with known cell cycle functions and included 59 lncRNAs. We selected four of these lncRNAs – AC005682.5, RP11-132A1.4, ZFAS1, and EPB41L4A-AS1 – for further experimental validation and found that knockdown of each of the four lncRNAs affected cell cycle phase distributions and reduced proliferation in multiple cell lines. These results show that many genes with cell cycle functions have concomitant cell-cycle dependent changes in promoter activity, transcription, and RNA levels and support that our multi-omics method is well suited for identifying lncRNAs involved in the cell cycle.

Iron Chelator ICL670 Inhibits HIV-1 Transcription.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3863-3863
Author(s):  
Zufan Debebe ◽  
Tatyana Ammosova ◽  
Hanspeter Nick ◽  
Xiaomei Niu ◽  
Marina Jerebtsova ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Protein Level ◽  
Iron Chelator ◽  
Iron Chelators ◽  
Cyclin T1 ◽  
Terminal Domain ◽  
Cycle Dependent ◽  
Hiv 1

Abstract HIV-1 replication is induced by the excess of iron and iron chelation by desferrioxamine (DFO) inhibits viral replication in HIV-1 infected CEM T cells [1]. Treatment of cells with DFO or 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone inhibits expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK2) [2]. HIV-1 transcription is activated by Tat protein, which recruits transcriptional co-activators to the HIV-1 promoter. Elongation of HIV-1 transcription is mediated by the interaction of HIV Tat with host cell cycle-dependent kinase 9 (CDK9)/cyclin T1, which phosphorylates the C-terminal domain of RNA polymerase II. Our recent studies showed that CDK2 participates in HIV-1 transcription by phosphorylating Tat [3]. Thus inhibition of CDK2 by iron chelators might present a new approach to inhibit HIV-1 transcription. We evaluated the effect of a clinically approved orally effective iron chelator, 4-[3,5-bis-(hydroxyphenyl) -1,2,4-triazol-1-yl]-benzoic acid (ICL670 or deferasirox) on HIV-1 transcription. ICL670 inhibited Tat-induced HIV-1 transcription in CEM, 293T and HeLa cells at concentrations that did not induce cytotoxicity. The chelator decreased cellular activity of CDK2 but not its protein level and reduced HIV-1 Tat phosphorylation by CDK2. ICL670 did not decrease CDK9 protein level but significantly reduced association of CDK9 with cyclin T1 and reduced phosphorylation of Ser-2 residues of RNA polymerase II C-terminal domain. In conclusion, our findings add to the evidence that iron chelators may inhibit HIV-1 transcription by deregulating CDK2 and Cdk9. Further consideration should be given to the evaluation of ICL670 for future anti-retroviral therapeutics and to the development of iron chelators specifically as anti-retroviral agents.

Flavopiridol Down-Regulates Genes Involved in Cell Cycle Regulation and Tumor Progression in Adults with Refractory or Poor-Risk Acute Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 953-953 ◽  
Author(s):  
Linda Resar ◽  
Joelle Hillion ◽  
Katrina Alino ◽  
Michelle Rudek ◽  
Judith Karp
Keyword(s):  
Cell Cycle ◽  
Acute Leukemia ◽  
Rna Polymerase ◽  
Cyclin D1 ◽  
Rna Polymerase Ii ◽  
Target Genes ◽  
Mrna Levels ◽  
Cyclin Dependent Kinase ◽  
Poor Risk ◽  
Before And After

Abstract Acute leukemia in adults continues to be a formidable clinical challenge that demands further investigation to identify more rational therapies. To optimize anti-leukemia therapy, we are investigating the prototypical cyclin dependent kinase (cdk) inhibitor, flavopiridol, in refractory or poor-risk disease. Flavopiridol is a cytotoxic molecule that is thought to induce cell cycle arrest by blocking cyclin-dependent kinase (cdk) function, thereby interfering with RNA Polymerase II activity and globally down-regulating gene expression. In the setting of pan-cdk inhibition, E2F1 is released and appears to drive apoptosis in transformed cells. Consistent with these proposed mechanisms of action, a previous study from our group showed that flavopiridol induces apoptosis in vitro in leukemic blasts from patients with refractory leukemia. Administration of flavopiridol was associated with a decrease in one or more of the following proteins in the leukemic blasts: RNA Polymerase II, STAT3, cyclin D1, Bcl-2, and Mcl-1. Serum VEGF levels also decreased in most patients. We are now investigating mRNA levels of the genes encoding these proteins by quantitative, RT-PCR in leukemic blasts from adult patients with refractory or poor-risk leukemia before and after flavopiridol therapy. We have treated 26 patients with flavopiridol at an escalating, hybrid dose followed by ara-c and mitxantrone. Adequate RNA from leukemic blasts before and after flavopiridol administration was available from 8 of 11 patients studied thus far. All cases (8/8) exhibit a marked decrease in mRNA for VEGF following flavopiridol. mRNA levels for other putative flavopiridol target genes is also decreased in a subset of leukemic blast samples after therapy, as follows: E2F1 (6/8), STAT3 (6/8), Mcl-1 (6/8), RNA Polymerase subunit 2a (3/3), and cyclin D1 (2/3). In contrast, bcl-2 mRNA levels increased after flavopiridol in most cases (7/8), which could represent a compensatory mechanism of leukemic blasts to avoid apoptotic cell death. Our preliminary studies indicate that flavopiridol is cytotoxic in poor-risk and refractory acute leukemia. Studies are underway to determine if down-regulation of any putative target genes correlates with pharmacologic data or clinical responses.

Changes in RNA polymerase II in a cell cycle-specific temperature-sensitive mutant of hamster cells

1980 ◽  
Vol 103 (1) ◽  
pp. 97-103 ◽  
Author(s):  
Mara Rossini ◽  
Susan Baserga ◽  
C. H. Huang ◽  
C. James Ingles ◽  
Renato Baserga
Keyword(s):  
Cell Cycle ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Temperature Sensitive ◽  
Sensitive Mutant ◽  
Temperature Sensitive Mutant ◽  
A Cell ◽  
Specific Temperature

scholarly journals Mitotic repression of RNA polymerase II transcription is accompanied by release of transcription elongation complexes.

1997 ◽  
Vol 17 (10) ◽  
pp. 5791-5802 ◽  
Author(s):  
G G Parsons ◽  
C A Spencer
Keyword(s):  
Cell Cycle ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Rna Synthesis ◽  
Transcription Elongation ◽  
Control Cell ◽  
Specific Gene ◽  
Mitotic Chromosomes ◽  
Transcription Repression ◽  
Rna Polymerase Ii Transcription

Nuclear RNA synthesis is repressed during the mitotic phase of each cell cycle. Although total RNA synthesis remains low throughout mitosis, the degree of RNA polymerase II transcription repression on specific genes has not been examined. In addition, it is not known whether mitotic repression of RNA polymerase II transcription is due to polymerase pausing or ejection of transcription elongation complexes from mitotic chromosomes. In this study, we show that RNA polymerase II transcription is repressed in mammalian cells on a number of specific gene regions during mitosis. We also show that the majority of RNA polymerase II transcription elongation complexes are physically excluded from mitotic chromosomes between late prophase and late telophase. Despite generalized transcription repression and stripping of RNA polymerase II complexes from DNA, arrested RNA polymerase II ternary complexes appear to remain on some gene regions during mitosis. The cyclic repression of transcription and ejection of RNA polymerase II transcription elongation complexes may help regulate the transcriptional events that control cell cycle progression and differentiation.

scholarly journals Localized phosphorylation of RNA Polymerase II by G1 cyclin-Cdk promotes cell cycle entry

2021 ◽  
Author(s):  
Mardo Koivomagi ◽  
Matthew P. Swaffer ◽  
Jonathan J. Turner ◽  
Georgi K Marinov ◽  
Jan M. Skotheim
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Cell Cycle Gene ◽  
Cyclin Dependent Kinases ◽  
Cell Cycle Entry ◽  
G1 Cyclin ◽  
Regulated Promoters ◽  
Cell Cycle Gene Expression

The cell cycle is thought to be initiated by cyclin-dependent kinases (Cdk) inactivating transcriptional inhibitors of cell cycle gene-expression. In budding yeast, the G1 cyclin Cln3-Cdk1 complex is thought to directly phosphorylate Whi5, thereby releasing the transcription factor SBF and committing cells to division. Here, we report that Cln3-Cdk1 does not phosphorylate Whi5, but instead phosphorylates the RNA Polymerase II subunit Rpb1 C-terminal domain (CTD) on S5 of its heptapeptide repeats. Cln3-Cdk1 binds SBF-regulated promoters and Cln3 function can be performed by the canonical S5 kinase Ccl1-Kin28 when synthetically recruited to SBF. Thus, Cln3-Cdk1 triggers cell division by phosphorylating Rpb1 at SBF-regulated promoters to activate transcription. Our findings blur the distinction between cell cycle and transcriptional Cdks to highlight the ancient relationship between these processes.

scholarly journals G 1 cyclin–Cdk promotes cell cycle entry through localized phosphorylation of RNA polymerase II

Science ◽  
2021 ◽  
Vol 374 (6565) ◽  
pp. 347-351 ◽  
Author(s):  
Mardo Kõivomägi ◽  
Matthew P. Swaffer ◽  
Jonathan J. Turner ◽  
Georgi Marinov ◽  
Jan M. Skotheim
Keyword(s):  
Cell Cycle ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Cell Cycle Entry

scholarly journals Inhibition of transcription blocks cell cycle progression of NIH3T3 fibroblasts specifically in G1

1993 ◽  
Vol 105 (1) ◽  
pp. 113-122 ◽  
Author(s):  
S. Adolph ◽  
S. Brusselbach ◽  
R. Muller
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Cell Cycle Progression ◽  
Video Recording ◽  
Cycle Progression ◽  
Nih3t3 Cells ◽  
Restriction Point ◽  
Alpha Amanitin

We have analysed the role of RNA polymerase II-dependent transcription in cell cycle progression. Time-lapse video recording and cytogenetic analysis were used to determine the sensitivity of NIH3T3 cells to the RNA polymerase II inhibitor alpha-amanitin at different stages of the cell cycle. Our results show that alpha-amanitin blocks cells specifically in G1, irrespective of the concentration within the range of 3 to 30 micrograms/ml. This indicates that transcription in G1 is required to overcome a restriction point located in this phase of the cell cycle. In agreement with this conclusion is the requirement for an uninhibited protein synthesis during G1 progression. In addition, the insensitivity of S-phase cells to RNA polymerase II inhibition suggests that the transcription of genes thought to be normally induced during S/G2 is not required for the completion of an ongoing cell cycle. S/G2 progression was however clearly dependent on protein synthesis. This suggests that cells exposed to alpha-amanitin are able to complete their cell cycle because sufficiently high levels of mRNA are present in S/G2 due to basal level transcription, or are left from preceding cell cycles. It is therefore unlikely that transcriptional regulation in S or G2 plays a crucial role in the control of cell cycle progression in NIH3T3 cells.

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