scholarly journals A novel auxin-inducible degron system for rapid, cell cycle-specific targeted proteolysis

2021 ◽  
Author(s):  
Marina Capece ◽  
Anna Tessari ◽  
Joseph Mills ◽  
Gian Luca Rampioni Vinciguerra ◽  
Chenyu Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Degradation ◽  
Cell Population ◽  
Target Proteins ◽  
Endogenous Gene ◽  
Protein Depletion ◽  
On Demand ◽  
Cell Synchronization ◽  
Cell Cycle Status ◽  
The Way

AbstractThe OsTIR1/auxin-inducible degron (AID) system allows “on demand” selective and reversible protein degradation upon exposure to the phytohormone auxin. In the current format, this technology does not allow to study the effect of acute protein depletion selectively in one phase of the cell cycle, as auxin similarly affects all the treated cells irrespectively of their proliferation status. Therefore, the AID system requires coupling with cell synchronization techniques, which can alter the basal biological status of the studied cell population. Here, we introduce a new AID system to Regulate OsTIR1 Levels based on the Cell Cycle Status (ROLECCS system), which induces proteolysis of both exogenously transfected and endogenous gene-edited targets in specific phases of the cell cycle. This new tool paves the way to studying the differential roles that target proteins may have in specific phases of the cell cycle.

Prawne aspekty eutanazji w Holandii

2016 ◽  
Vol 14 (3) ◽  
pp. 243-253
Author(s):  
Grzegorz Stefanowicz
Keyword(s):  
The Netherlands ◽  
Assisted Suicide ◽  
Public Authority ◽  
Dutch Society ◽  
On Demand ◽  
Limited Length ◽  
The Law ◽  
Death On Demand ◽  
The Way

This article undertakes to show the way that has led to the statutory decriminalization of euthanasia-related murder and assisted suicide in the Kingdom of the Netherlands. It presents the evolution of the views held by Dutch society on the euthanasia related practice, in the consequence of which death on demand has become legal after less than thirty years. Due attention is paid to the role of organs of public authority in these changes, with a particular emphasis put on the role of the Dutch Parliament – the States General. Because of scarcity of space and limited length of the article, the change in the attitudes toward euthanasia, which has taken place in the Netherlands, is presented in a synthetic way – from the first discussions on admissibility of a euthanasia-related murder carried out in the 1970s, through the practice of killing patients at their request, which was against the law at that time, but with years began more and more acceptable, up to the statutory decriminalization of euthanasia by the Dutch Parliament, made with the support of the majority of society.

scholarly journals Immune regulation of in vitro murine megakaryocyte development. Role of T lymphocytes and Ia antigen expression.

1985 ◽  
Vol 162 (6) ◽  
pp. 2053-2067 ◽  
Author(s):  
M W Long ◽  
D N Shapiro
Keyword(s):  
Cell Cycle ◽  
T Cell ◽  
T Lymphocytes ◽  
Progenitor Cells ◽  
Immune Modulation ◽  
Immune Recognition ◽  
Activated T Cells ◽  
Ia Antigen ◽  
Cell Cycle Status

Mitogen-activated murine T lymphocytes or T cell hybridomas produce an activity (megakaryocyte [Mk] potentiator activity) that enhances the in vitro growth and development of Mk colonies. This activity was found in optimal concentrations (2.5%) in T cell hybridoma-conditioned medium, and was also produced by feeder layers of concanavalin A-activated T cells. A subpopulation of murine Mk progenitor cells (colony-forming units; CFU-Mk) bears the Ia antigen. Separate experiments indicated that T cell products stimulate CFU-Mk by increasing their basal levels of Ia expression as well as the frequency of cells actively synthesizing DNA. The hypothesis that the expression of this antigen was related to the cell cycle status of these progenitor cells was confirmed in studies that indicated that ablation of actively cycling cells in vivo abrogated the cytotoxic effects of anti-Ia monoclonal antibodies. The interdependence of T cell lymphokine regulation of both Ia expression and cell cycle status was also seen in in vitro experiments in which Ia+ progenitor cells were eliminated by complement-dependent cytotoxicity. The removal of Ia+ cells prevented 5-hydroxyurea-mediated inhibition of cells in S phase. We hypothesize that immune modulation of megakaryocytopoiesis occurs via soluble T cell products that augment Mk differentiation. Further, the mechanism of immune recognition/modulation may occur via Ia antigens present on the surface of these progenitor cells.

In vitro evidence that LHRH stimulates the recruitment of prolactin mRNA-expressing cells during the postnatal period in the rat

1994 ◽  
Vol 12 (1) ◽  
pp. 107-118 ◽  
Author(s):  
A Van Bael ◽  
R Huygen ◽  
B Himpens ◽  
C Denef
Keyword(s):  
Cell Cycle ◽  
Cell Population ◽  
Blot Hybridization ◽  
Postnatal Period ◽  
S Phase ◽  
Female Rats ◽  
Mrna Levels ◽  
Dot Blot ◽  
Total Cell Population

ABSTRACT We have studied the effect of LHRH and neuropeptide Y (NPY) on prolactin (PRL) mRNA levels in pituitary reaggregate cell cultures from 14-day-old female rats, by means of in situ hybridization and Northern blot analysis. As estimated by computer-image analysis, addition of LHRH on day 5 in culture for 40 h resulted in a 37% increase in the total cytoplasmic areas of cells containing PRL mRNA, visualized using a digoxigenin-labelled PRL cRNA. The size of individual PRL-expressing cells was not influenced, nor was the content of PRL mRNA per cell. A similar effect of LHRH was found by dot blot hybridization of extracted RNA. PRL mRNA levels were not affected by NPY. LHRH induced a 29% increase in the number of PRL mRNA-expressing cells processing through the S phase of the cell cycle, visualized by the incorporation of [3H]thymidine ([3H]T) into DNA over 16 h. The fraction of [3H]T-labelled cells was 10–12% of the total cell population. NPY did not influence the number of [3H]T-positive cells expressing PRL mRNA, but completely blocked the effect of LHRH on the latter population. The present data suggest that LHRH, probably via a paracrine action of gonadotrophs, stimulates the recruitment of new lactotrophs, an action which is negatively modulated by NPY. Since the magnitude of this effect was the same in the total pituitary cell population as in cells processing through the S phase of the cell cycle and presumably mitosis, recruitment of lactotrophs seems to be based on differentiation of progenitor or immature cells into PRL-expressing cells, rather than on a mitogenic action on pre-existing lactotrophs alone.

scholarly journals JunB Breakdown in Mid-/Late G2 Is Required for Down-Regulation of Cyclin A2 Levels and Proper Mitosis

2008 ◽  
Vol 28 (12) ◽  
pp. 4173-4187 ◽  
Author(s):  
Rosa Farràs ◽  
Véronique Baldin ◽  
Sandra Gallach ◽  
Claire Acquaviva ◽  
Guillaume Bossis ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Genetic Instability ◽  
S Phase ◽  
Subsequent Reduction ◽  
Suppressor Activity ◽  
Cell Synchronization ◽  
Tumor Suppressor Activity ◽  
A Cell ◽  
Cyclin A2

ABSTRACT JunB, a member of the AP-1 family of dimeric transcription factors, is best known as a cell proliferation inhibitor, a senescence inducer, and a tumor suppressor, although it also has been attributed a cell division-promoting activity. Its effects on the cell cycle have been studied mostly in G1 and S phases, whereas its role in G2 and M phases still is elusive. Using cell synchronization experiments, we show that JunB levels, which are high in S phase, drop during mid- to late G2 phase due to accelerated phosphorylation-dependent degradation by the proteasome. The forced expression of an ectopic JunB protein in late G2 phase indicates that JunB decay is necessary for the subsequent reduction of cyclin A2 levels in prometaphase, the latter event being essential for proper mitosis. Consistently, abnormal JunB expression in late G2 phase entails a variety of mitotic defects. As these aberrations may cause genetic instability, our findings contrast with the acknowledged tumor suppressor activity of JunB and reveal a mechanism by which the deregulation of JunB might contribute to tumorigenesis.

Small-molecule degraders of cyclin-dependent kinase protein: a review

2021 ◽  
Author(s):  
Bin Yu ◽  
Zekun Du ◽  
Yuming Zhang ◽  
Zhiyu Li ◽  
Jinlei Bian
Keyword(s):  
Cell Cycle ◽  
Drug Resistance ◽  
Protein Degradation ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Structural Characteristics ◽  
Protein A ◽  
Cyclin Dependent Kinase ◽  
Chemical Tools ◽  
Potential Therapeutics

Proteolysis-targeting chimeras are a new modality of chemical tools and potential therapeutics involving the induction of protein degradation. Cyclin-dependent kinase (CDK) protein, which is involved in cycles and transcription cycles, participates in regulation of the cell cycle, transcription and splicing. Proteolysis-targeting chimeras targeting CDKs show several advantages over traditional CDK small-molecule inhibitors in potency, selectivity and drug resistance. In addition, the discovery of molecule glues promotes the development of CDK degraders. Herein, the authors describe the existing CDK degraders and focus on the discussion of the structural characteristics and design of these degraders.

scholarly journals Differences in Cell Cycle Status Underlie Transcriptional Heterogeneity in the HSC Compartment

Cell Reports ◽  
2018 ◽  
Vol 24 (3) ◽  
pp. 766-780 ◽  
Author(s):  
Felicia Kathrine Bratt Lauridsen ◽  
Tanja Lyholm Jensen ◽  
Nicolas Rapin ◽  
Derya Aslan ◽  
Anna Sofia Wilhelmson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Status
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