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.

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 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 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

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

scholarly journals Low phosphate signaling induces changes in cell cycle gene expression by increasing auxin sensitivity in the Arabidopsis root system

2009 ◽  
Vol 4 (8) ◽  
pp. 781-783 ◽  
Author(s):  
Claudia-Anahí Pérez-Torres ◽  
José López-Bucio ◽  
Luis Herrera Estrella
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Root System ◽  
Cell Cycle Gene ◽  
Arabidopsis Root ◽  
Cell Cycle Gene Expression

scholarly journals Temporal Control of Cell Cycle Gene Expression Mediated by E2F Transcription Factors

Cell Cycle ◽  
2005 ◽  
Vol 4 (5) ◽  
pp. 633-636 ◽  
Author(s):  
Wencheng Zhu ◽  
Paloma H. Giangrande ◽  
Joseph R. Nevins
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factors ◽  
Cell Cycle Gene ◽  
Temporal Control ◽  
E2f Transcription Factors ◽  
Cell Cycle Gene Expression

scholarly journals Altered Cell Cycle Gene Expression and Apoptosis in Post-Implantation Dog Parthenotes

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e41256 ◽  
Author(s):  
Jung Eun Park ◽  
Min Jung Kim ◽  
Seung Kwon Ha ◽  
So Gun Hong ◽  
Hyun Ju Oh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Gene ◽  
Altered Cell ◽  
Post Implantation ◽  
Cell Cycle Gene Expression
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