scholarly journals A toxin-antitoxin system associated transcription factor of Caulobacter crescentus can influence cell cycle-regulated gene expression during the SOS response

2020 ◽  
Author(s):  
Koyel Ghosh ◽  
Kamilla Ankær Brejndal ◽  
Clare L. Kirkpatrick
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Dna Damage ◽  
Transcription Factor ◽  
Caulobacter Crescentus ◽  
Sos Response ◽  
Cell Cycle Gene ◽  
Regulated Gene Expression ◽  
Cell Cycle Gene Expression

AbstractToxin-antitoxin (TA) systems are widespread in bacterial chromosomes but their functions remain enigmatic. Although many are transcriptionally upregulated by stress conditions, it is unclear what role they play in cellular responses to stress and to what extent the role of a given TA system homologue varies between different bacterial species. In this work we investigate the role of the DNA damage-inducible TA system HigBA of Caulobacter crescentus in the SOS response and discover that in addition to the toxin HigB affecting cell cycle gene expression through inhibition of the master regulator CtrA, HigBA possesses a transcription factor third component, HigC, which both auto-regulates the TA system and acts independently of it. Through HigC, the system exerts downstream effects on antibiotic (ciprofloxacin) resistance and cell cycle gene expression. HigB and HigC had inverse effects on cell cycle gene regulation, with HigB reducing and HigC increasing the expression of CtrA-dependent promoters. Neither HigBA nor HigC had any effect on formation of persister cells in response to ciprofloxacin. Rather, their role in the SOS response appears to be as transcriptional and post-transcriptional regulators of cell cycle-dependent gene expression, transmitting the status of the SOS response as a regulatory input into the cell cycle control network via CtrA.ImportanceAlmost all bacteria respond to DNA damage by upregulating a set of genes that helps them to repair and recover from the damage, known as the SOS response. The set of genes induced during the SOS response varies between species, but frequently includes toxin-antitoxin systems. However, it is unknown what the consequence of inducing these systems is, and whether they provide any benefit to the cells. We show here that the DNA damage-induced TA system HigBA of the asymmetrically dividing bacterium Caulobacter crescentus affects the cell cycle regulation of this bacterium. HigBA also has a transcription factor encoded immediately downstream of it, named here HigC, which controls expression of the TA system and potentially other genes as well. Therefore, this work identifies a new role for TA systems in the DNA damage response, distinct from non-specific stress tolerance mechanisms which had been proposed previously.

scholarly journals Cyclin F drives proliferation through SCF-dependent degradation of the retinoblastoma-like tumor suppressor p130/RBL2

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Taylor P Enrico ◽  
Wayne Stallaert ◽  
Elizaveta T Wick ◽  
Peter Ngoi ◽  
Xianxi Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cell Cycle Control ◽  
Cell Cycle Gene ◽  
E3 Ligases ◽  
Gene Transcripts ◽  
Cyclin F ◽  
Cell Cycle Gene Expression

Cell cycle gene expression programs fuel proliferation and are universally dysregulated in cancer. The retinoblastoma (RB)-family of proteins, RB1, RBL1/p107 and RBL2/p130, coordinately repress cell cycle gene expression, inhibiting proliferation and suppressing tumorigenesis. Phosphorylation of RB-family proteins by cyclin dependent kinases is firmly established. Like phosphorylation, ubiquitination is essential to cell cycle control, and numerous proliferative regulators, tumor suppressors, and oncoproteins are ubiquitinated. However, little is known about the role of ubiquitin signaling in controlling RB-family proteins. A systems genetics analysis of CRISPR/Cas9 screens suggested the potential regulation of the RB-network by cyclin F, a substrate recognition receptor for the SCF family of E3 ligases. We demonstrate that RBL2/p130 is a direct substrate of SCFcyclin F. We map a cyclin F regulatory site to a flexible linker in the p130 pocket domain, and show that this site mediates binding, stability, and ubiquitination. Expression of a mutant version of p130, which cannot be ubiquitinated, severely impaired proliferative capacity and cell cycle progression. Consistently, we observed reduced expression of cell cycle gene transcripts, as well a reduced abundance of cell cycle proteins, analyzed by quantitative, iterative immunofluorescent imaging. These data suggest a key role for SCFcyclin F in the CDK-RB network and raise the possibility that aberrant p130 degradation could dysregulate the cell cycle in human cancers.

scholarly journals Tissue-specific actions of Pax6 on proliferation-differentiation balance in the developing forebrain are Foxg1-dependent

2018 ◽  
Author(s):  
Idoia Quintana-Urzainqui ◽  
Zrinko Kozić ◽  
Soham Mitra ◽  
Tian Tian ◽  
Martine Manuel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Cell Cycle Gene ◽  
Tissue Specific ◽  
Proliferation And Differentiation ◽  
Multiple Regions ◽  
Cell Cycle Gene Expression

SummaryDifferences in the growth and maturation of diverse forebrain tissues depends on region-specific transcriptional regulation. Individual transcription factors act simultaneously in multiple regions that develop very differently, raising questions about the extent to which their actions vary regionally. We found that the transcription factor Pax6 affects the transcriptomes and the balance between proliferation and differentiation in opposite directions in murine diencephalon versus cortex. We tested several possible mechanisms to explain Pax6’s tissue-specific actions and found that the presence of the transcription factor Foxg1 in cortex but not diencephalon was most influential. We found that Foxg1 is responsible for many of the differences in cell cycle gene expression between diencephalon and cortex. In cortex lacking Foxg1, Pax6’s action on the balance of proliferation versus differentiation became diencephalon-like. Our findings reveal a mechanism for generating regional forebrain diversity in which the actions of one transcription factor completely reverse the actions of another.

scholarly journals Regulation of a transcription factor network by Cdk1 coordinates late cell cycle gene expression

2014 ◽  
Vol 33 (9) ◽  
pp. 1044-1060 ◽  
Author(s):  
B. D. Landry ◽  
C. E. Mapa ◽  
H. E. Arsenault ◽  
K. E. Poti ◽  
J. A. Benanti
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factor ◽  
Cell Cycle Gene ◽  
Transcription Factor Network ◽  
Cell Cycle Gene Expression

scholarly journals Role of a Candida albicans Nrm1/Whi5 homologue in cell cycle gene expression and DNA replication stress response

2012 ◽  
Vol 84 (4) ◽  
pp. 778-794 ◽  
Author(s):  
Ayala Ofir ◽  
Kay Hofmann ◽  
Esther Weindling ◽  
Tsvia Gildor ◽  
Katherine S. Barker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Candida Albicans ◽  
Dna Replication ◽  
Stress Response ◽  
Replication Stress ◽  
Cell Cycle Gene ◽  
Dna Replication Stress ◽  
Cell Cycle Gene Expression

scholarly journals Cyclin F drives proliferation through SCF-dependent degradation of the retinoblastoma-like tumor suppressor p130/RBL2

2021 ◽  
Author(s):  
Taylor P. Enrico ◽  
Wayne Stallaert ◽  
Elizaveta T. Wick ◽  
Peter Ngoi ◽  
Seth M. Rubin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Control ◽  
Cell Cycle Gene ◽  
Loss Of Function ◽  
E3 Ligases ◽  
Dependent Protein ◽  
Cyclin F ◽  
Cell Cycle Gene Expression

AbstractCell cycle gene expression programs fuel proliferation and are dysregulated in many cancers. The retinoblastoma-family proteins, RB, p130/RBL2 and p107/RBL1, coordinately repress cell cycle gene expression, inhibiting proliferation and suppressing tumorigenesis. Ubiquitin-dependent protein degradation is essential to cell cycle control, and numerous proliferative regulators, tumor suppressors, and oncoproteins are ubiquitinated. However, little is known about the role of ubiquitin signaling in controlling RB-family proteins. A systems genetics analysis of several hundred CRISPR/Cas9 loss-of-function screens suggested the potential regulation of the RB-network by cyclin F, a substrate recognition receptor for the SCF family of E3 ligases. We demonstrate that RBL2/p130 is a direct substrate of SCFcyclin F. We map a cyclin F regulatory site to a flexible linker in the p130 pocket domain, and show that this site mediates binding, stability, and ubiquitination. Expression of a non-degradable p130 represses cell cycle gene expression and strongly reduces proliferation. These data suggest that SCFcyclin Fplays a key role in the CDK-RB network and raises the possibility that aberrant p130 degradation could dysregulate the cell cycle in human cancers.

Ethanol alters cell cycle gene expression in human embryonic stem cells

2016 ◽  
Vol 01 (03) ◽  
pp. 201-208 ◽  
Author(s):  
Malini Krishnamoorthy ◽  
Brian Gerwe ◽  
Jamie Heimburg-Molinaro ◽  
Rachel Nash ◽  
Jagan Arumugham ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Cell Cycle Gene ◽  
Cell Cycle Gene Expression

Dissecting the Role of Thyrotropin in the DNA Damage Response in Human Thyrocytes after 131I, γ Radiation and H2O2

2019 ◽  
Vol 105 (3) ◽  
pp. 839-853
Author(s):  
Aglaia Kyrilli ◽  
David Gacquer ◽  
Vincent Detours ◽  
Anne Lefort ◽  
Frédéric Libert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Iodide Uptake ◽  
Transcriptomic Response ◽  
Uptake Inhibition ◽  
Γ Radiation ◽  
Damage Response

Abstract Background The early molecular events in human thyrocytes after 131I exposure have not yet been unravelled. Therefore, we investigated the role of TSH in the 131I-induced DNA damage response and gene expression in primary cultured human thyrocytes. Methods Following exposure of thyrocytes, in the presence or absence of TSH, to 131I (β radiation), γ radiation (3 Gy), and hydrogen peroxide (H2O2), we assessed DNA damage, proliferation, and cell-cycle status. We conducted RNA sequencing to profile gene expression after each type of exposure and evaluated the influence of TSH on each transcriptomic response. Results Overall, the thyrocyte responses following exposure to β or γ radiation and to H2O2 were similar. However, TSH increased 131I-induced DNA damage, an effect partially diminished after iodide uptake inhibition. Specifically, TSH increased the number of DNA double-strand breaks in nonexposed thyrocytes and thus predisposed them to greater damage following 131I exposure. This effect most likely occurred via Gα q cascade and a rise in intracellular reactive oxygen species (ROS) levels. β and γ radiation prolonged thyroid cell-cycle arrest to a similar extent without sign of apoptosis. The gene expression profiles of thyrocytes exposed to β/γ radiation or H2O2 were overlapping. Modulations in genes involved in inflammatory response, apoptosis, and proliferation were observed. TSH increased the number and intensity of modulation of differentially expressed genes after 131I exposure. Conclusions TSH specifically increased 131I-induced DNA damage probably via a rise in ROS levels and produced a more prominent transcriptomic response after exposure to 131I.

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