scholarly journals Cell cycle oscillators underlying orderly proteolysis of E2F8

2019 ◽  
Author(s):  
Danit Wasserman ◽  
Sapir Nachum ◽  
Meital Cohen ◽  
Taylor P Enrico ◽  
Meirav Noach-Hirsh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ubiquitin Ligase ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Dynamic Cell ◽  
G2 Phase ◽  
Differential Stability ◽  
Complementary Set ◽  
Cyclin F ◽  
Transcription Factor E2f1

AbstractE2F8 is a transcriptional repressor that antagonizes the canonical cell cycle transcription factor E2F1. Despite the importance of this atypical E2F family member in cell cycle, apoptosis and cancer, we lack a complete description of the mechanisms that control its dynamics. To address this question, we developed a complementary set of static and dynamic cell-free systems of human origin, which recapitulate inter-mitotic and G1 phases, and a full transition from pro-metaphase to G1. This revealed an interlocking molecular switch controlling E2F8 degradation at mitotic exit, involving dephosphorylation of Cdk1 sites in E2F8 and the activation of APC/CCdh1, but not APC/CCdc20. Further, we revealed a differential stability of E2F8, accounting for its accumulation in late G1 while APC/CCdh1 is still active and suggesting a key role for APC/C in controlling G1-S transcription. Finally, we identified SCF-Cyclin F as the ubiquitin ligase controlling E2F8 in G2-phase. Altogether, our data provide new insights into the regulation of E2F8 throughout the cell cycle, illuminating an extensive coordination between phosphorylation, ubiquitination and transcription in promoting orderly cell cycle progression.

scholarly journals Cubic Membranes Formation in Synchronized Human Hepatocellular Carcinoma Cells Reveals a Possible Role as a Structural Antioxidant Defense System in Cell Cycle Progression

2020 ◽  
Vol 8 ◽  
Author(s):  
Deqin Kong ◽  
Rui Liu ◽  
Jiangzheng Liu ◽  
Qingbiao Zhou ◽  
Jiaxin Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Carcinoma Cells ◽  
Human Hepatocellular Carcinoma ◽  
Cycle Progression ◽  
Hepatocellular Carcinoma Cells ◽  
G2 Phase ◽  
Human Hepatocellular Carcinoma Cells

Cubic membranes (CMs) represent unique biological membrane structures with highly curved three-dimensional periodic minimal surfaces, which have been observed in a wide range of cell types and organelles under various stress conditions (e. g., starvation, virus-infection, and oxidation). However, there are few reports on the biological roles of CMs, especially their roles in cell cycle. Hence, we established a stable cell population of human hepatocellular carcinoma cells (HepG2) of 100% S phase by thymidine treatment, and determined certain parameters in G2 phase released from S phase. Then we found a close relationship between CMs formation and cell cycle, and an increase in reactive oxygen species (ROS) and mitochondrial function. After the synchronization of HepG2 cells were induced, CMs were observed through transmission electron microscope in G2 phase but not in G1, S and M phase. Moreover, the increased ATP production, mitochondrial and intracellular ROS levels were also present in G2 phase, which demonstrated a positive correlation with CMs formation by Pearson correlation analysis. This study suggests that CMs may act as an antioxidant structure in response to mitochondria-derived ROS during G2 phase and thus participate in cell cycle progression.

scholarly journals DNA Damage during G2 Phase Does Not Affect Cell Cycle Progression of the Green Alga Scenedesmus quadricauda

PLoS ONE ◽  
2011 ◽  
Vol 6 (5) ◽  
pp. e19626 ◽  
Author(s):  
Monika Hlavová ◽  
Mária Čížková ◽  
Milada Vítová ◽  
Kateřina Bišová ◽  
Vilém Zachleder
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Green Alga ◽  
Cell Cycle Progression ◽  
Scenedesmus Quadricauda ◽  
Cycle Progression ◽  
Affect Cell Cycle Progression ◽  
G2 Phase ◽  
Alga Scenedesmus Quadricauda

scholarly journals HIV-1 Vif promotes the G1- to S-phase cell-cycle transition

Blood ◽  
2011 ◽  
Vol 117 (4) ◽  
pp. 1260-1269 ◽  
Author(s):  
Jiangfang Wang ◽  
Emma L. Reuschel ◽  
Jason M. Shackelford ◽  
Lauren Jeang ◽  
Debra K. Shivers ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Phase Cell ◽  
Small Interfering Rnas ◽  
Cycle Progression ◽  
Viral Infectivity Factor ◽  
G2 Phase ◽  
Regulate Cell Cycle Progression ◽  
Hiv 1

AbstractHIV-1 depends on host-cell resources for replication, access to which may be limited to a particular phase of the cell cycle. The HIV-encoded proteins Vpr (viral protein R) and Vif (viral infectivity factor) arrest cells in the G2 phase; however, alteration of other cell-cycle phases has not been reported. We show that Vif drives cells out of G1 and into the S phase. The effect of Vif on the G1-to-S transition is distinct from its effect on G2, because G2 arrest is Cullin5-dependent, whereas the G1-to-S progression is Cullin5-independent. Using mass spectrometry, we identified 2 novel cellular partners of Vif, Brd4 and Cdk9, both of which are known to regulate cell-cycle progression. We confirmed the interaction of Vif and Cdk9 by immunoprecipitation and Western blot, and showed that small interfering RNAs (siRNAs) specific for Cdk9 inhibit the Vif-mediated G1-to-S transition. These data suggest that Vif regulates early cell-cycle progression, with implications for infection and latency.

scholarly journals Cyclin F-Chk1 synthetic lethality mediated by E2F1 degradation

2019 ◽  
Author(s):  
Kamila Burdova ◽  
Hongbin Yang ◽  
Roberta Faedda ◽  
Samuel Hume ◽  
Daniel Ebner ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Kinase Inhibitors ◽  
Synthetic Lethality ◽  
Checkpoint Inhibitors ◽  
Dependent Manner ◽  
Cycle Progression ◽  
Multiple Substrates ◽  
Cyclin F

SummaryCyclins are central engines of cell cycle progression when partnered with Cyclin Dependent Kinases (CDKs). Among the different cyclins controlling cell cycle progression, cyclin F does not partner with a CDK, but forms an E3 ubiquitin ligase, assembling through the F-box domain, an Skp1-Cul1-F-box (SCF) module. Although multiple substrates of cyclin F have been identified the vulnerabilities of cells lacking cyclin F are not known. Thus, we assessed viability of cells lacking cyclin F upon challenging cells with more than 200 kinase inhibitors. The screen revealed a striking synthetic lethality between Chk1 inhibition and cyclin F loss. Chk1 inhibition in cells lacking cyclin F leads to DNA replication catastrophe. The DNA replication catastrophe depends on the accumulation of E2F1 in cyclin F depleted cells. We observe that SCFcyclin F promotes E2F1 degradation after Chk1 inhibitors in a CDK dependent manner. Thus, Cyclin F restricts E2F1 activity during cell cycle and upon checkpoint inhibition to prevent DNA replication stress. Our findings pave the way for patient selection in the clinical use of checkpoint inhibitors.

The CRL2LRR-1 ubiquitin ligase regulates cell cycle progression during C. elegans development.

2010 ◽  
Vol 123 (22) ◽  
pp. e1-e1
Author(s):  
J. Merlet ◽  
J. Burger ◽  
N. Tavernier ◽  
B. Richaudeau ◽  
J.-E. Gomes ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ubiquitin Ligase ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
C Elegans

scholarly journals The E3 ubiquitin ligase HECTD1 contributes to cell cycle progression through an effect on mitosis

2021 ◽  
Author(s):  
Natalie Vaughan ◽  
Nico Scholz ◽  
Catherine Lindon ◽  
Julien D, F Licchesi
Keyword(s):  
Cell Cycle ◽  
Ubiquitin Ligase ◽  
Cell Cycle Progression ◽  
Spindle Assembly Checkpoint ◽  
Time Lapse ◽  
Ubiquitin Chain ◽  
Cycle Progression ◽  
Anaphase Onset ◽  
Ubiquitin Ligase Activity ◽  
Complex Protein

Mechanistic studies of how protein ubiquitylation regulates the cell cycle, in particular during mitosis, has provided unique insights which have contributed to the emergence of the Ubiquitin code. In contrast to RING E3 ubiquitin ligases such as the APC/c ligase complex, the contribution of other E3 ligase families during cell cycle progression remains less well understood. Similarly, the contribution of ubiquitin chain types beyond homotypic K48 chains in S-phase or branched K11/K48 chains assembled by APC/c during mitosis, also remains to be fully determined. Our recent findings that HECTD1 ubiquitin ligase activity assembles branched K29/K48 ubiquitin linkages prompted us to evaluate its function during the cell cycle. We used transient knockdown and genetic knockout to show that HECTD1 depletion in HEK293T and HeLa cells decreases cell proliferation and we established that this is mediated through loss of its ubiquitin ligase activity. Interestingly, we found that HECTD1 depletion increases the proportion of cells with aligned chromosomes (Prometa/Metaphase). We confirmed this molecularly using phospho-Histone H3 (Ser28) as a marker of mitosis. Time-lapse microscopy of NEBD to anaphase onset established that HECTD1-depleted cells take on average longer to go through mitosis. To explore the mechanisms involved, we used proteomics to explore the endogenous HECTD1 interactome in mitosis and validated the Mitosis Checkpoint Complex protein BUB3 as a novel HECTD1 interactor. In line with this, we found that HECTD1 depletion reduces the activity of the Spindle Assembly Checkpoint. Overall, our data suggests a novel role for HECTD1 ubiquitin ligase activity in mitosis.

The ERK-RSK1 activation by growth factors at G2 phase delays cell cycle progression and reduces mitotic aberrations

2008 ◽  
Vol 20 (7) ◽  
pp. 1349-1358 ◽  
Author(s):  
Hyun-Ja Nam ◽  
Sujeong Kim ◽  
Min-Woo Lee ◽  
Bok-Soon Lee ◽  
Toshihiro Hara ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factors ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
G2 Phase

scholarly journals Transient expression of RAD51 in the late G2-phase is required for cell cycle progression in synchronousPhysarumcells

2014 ◽  
Vol 19 (10) ◽  
pp. 755-765 ◽  
Author(s):  
Anthony Le Cigne ◽  
Vanessa Menil-Philippot ◽  
Fabrice Fleury ◽  
Masayuki Takahashi ◽  
Christophe Thiriet
Keyword(s):  
Cell Cycle ◽  
Transient Expression ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
G2 Phase
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