scholarly journals Multisite phosphorylation by Cdk1 initiates delayed negative feedback to control mitotic transcription

2021 ◽  
Author(s):  
Jonathan B. Asfaha ◽  
Mihkel Örd ◽  
Mart Loog ◽  
David O. Morgan
Keyword(s):  
Gene Expression ◽  
Negative Feedback ◽  
Transcriptional Activation ◽  
Mitotic Arrest ◽  
Cyclin Dependent Kinase ◽  
Feedback Circuit ◽  
Mitotic Progression ◽  
Transcriptional Program ◽  
Multisite Phosphorylation ◽  
Negative Feedback Circuit

AbstractOrdered phosphorylation of cyclin-dependent kinase (CDK) substrates leads to the sequential transcriptional activation and inhibition of hundreds of cell cycle-regulated genes. We find that Ndd1, an activator of genes required for mitotic progression, is both positively and negatively regulated by CDK activity. CDK activity initially stimulates Ndd1-dependent transcription as cells enter mitosis, but prolonged high CDK activity in a mitotic arrest inhibits transcription. The result is a time-delayed negative feedback circuit that generates a pulse of mitotic gene expression. Our results suggest that high CDK activity catalyzes the formation of multiple weak phosphodegrons on Ndd1, leading to its destabilization. Cyclin specificity and phosphorylation kinetics contribute to the timing of Ndd1 destruction. Failure to degrade Ndd1 in a mitotic arrest leads to elevated mitotic gene expression. We conclude that a combination of positive and negative Ndd1 regulation by CDKs governs the timing and magnitude of the mitotic transcriptional program.

scholarly journals Stb1 Collaborates with Other Regulators To Modulate the G1-Specific Transcriptional Circuit

2008 ◽  
Vol 28 (22) ◽  
pp. 6919-6928 ◽  
Author(s):  
Robertus A. M. de Bruin ◽  
Tatyana I. Kalashnikova ◽  
Curt Wittenberg
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Histone Deacetylase ◽  
Negative Feedback ◽  
Transcriptional Activation ◽  
Budding Yeast ◽  
Cyclin Dependent Kinase ◽  
Stable Component ◽  
Dependent Inactivation ◽  
Transcriptional Induction

ABSTRACT G1-specific transcription in the budding yeast Saccharomyces cerevisiae depends upon SBF and MBF. Whereas inactivation of SBF-regulated genes during the G1/S transition depends upon mitotic B-type cyclins, inactivation of MBF has been reported to involve multiple regulators, Nrm1 and Stb1. Nrm1 is a transcriptional corepressor that inactivates MBF-regulated transcription via negative feedback as cells exit G1 phase. Cln/cyclin-dependent kinase (CDK)-dependent inactivation of Stb1, identified via its interaction with the histone deacetylase (HDAC) component Sin3, has also been reported to inactivate MBF-regulated transcription. This report shows that Stb1 is a stable component of both SBF and MBF that binds G1-specific promoters via Swi6 during G1 phase. It is important for the growth of cells in which SBF or MBF is inactive. Although dissociation of Stb1 from promoters as cells exit G1 correlates with Stb1 phosphorylation, phosphorylation is only partially dependent upon Cln1/2 and is not involved in transcription inactivation. Inactivation depends upon Nrm1 and Clb/CDK activity. Stb1 inactivation dampens maximal transcriptional induction during late G1 phase and also derepresses gene expression in G1-phase cells prior to Cln3-dependent transcriptional activation. The repression during G1 also depends upon Sin3. We speculate that the interaction between Stb1 and Sin3 regulates the Sin3/HDAC complex at G1-specific promoters.

scholarly journals Highly Sensitive Whole-Cell Biosensor for Cadmium Detection Based on a Negative Feedback Circuit

2021 ◽  
Vol 9 ◽  
Author(s):  
Guangbao Zhang ◽  
Shuting Hu ◽  
Xiaoqiang Jia
Keyword(s):  
Sensitivity And Specificity ◽  
Negative Feedback ◽  
Output Signal ◽  
World Health ◽  
Real Field ◽  
Feedback Circuit ◽  
Whole Cell ◽  
Feedback Amplifier ◽  
Cadmium Detection ◽  
Negative Feedback Circuit

Although many whole-cell biosensors (WCBs) for the detection of Cd2+ have been developed over the years, most lack sensitivity and specificity. In this paper, we developed a Cd2+ WCB with a negative feedback amplifier in P. putida KT2440. Based on the slope of the linear detection curve as a measure of sensitivity, WCB with negative feedback amplifier greatly increased the output signal of the reporter mCherry, resulting in 33% greater sensitivity than in an equivalent WCB without the negative feedback circuit. Moreover, WCB with negative feedback amplifier exhibited increased Cd2+ tolerance and a lower detection limit of 0.1 nM, a remarkable 400-fold improvement compared to the WCB without the negative feedback circuit, which is significantly below the World Health Organization standard of 27 nM (0.003 mg/L) for cadmium in drinking water. Due to the superior amplification of the output signal, WCB with negative feedback amplifier can provide a detectable signal in a much shorter time, and a fast response is highly preferable for real field applications. In addition, the WCB with negative feedback amplifier showed an unusually high specificity for Cd2+ compared to other metal ions, giving signals with other metals that were between 17.6 and 41.4 times weaker than with Cd2+. In summary, the negative feedback amplifier WCB designed in this work meets the requirements of Cd2+ detection with very high sensitivity and specificity, which also demonstrates that genetic negative feedback amplifiers are excellent tools for improving the performance of WCBs.

scholarly journals Modeling PLL Loop with Nonlinearity

Telecom IT ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 9-14
Author(s):  
Y. Nikitin ◽  
G. Tsygankov
Keyword(s):  
Nonlinear Model ◽  
Negative Feedback ◽  
Phase Locked Loop ◽  
Phase Detector ◽  
Stationary Mode ◽  
Voltage Controlled Oscillator ◽  
Feedback Circuit ◽  
Pulse Counter ◽  
Pulse Phase ◽  
Negative Feedback Circuit

A model of a pulse phase-locked loop multiplying ring in a MicroCap11 medium is considered. The analysis uses a nonlinear model of a voltage-controlled oscillator with a user-defined control characteristic. An RS-trigger is used as a pulse-phase detector, a pulse counter in the negative feedback circuit is implemented on JK-triggers. Transient processes in the ring, as well as the spectrum of the output oscillations in the steady (stationary) mode are considered.

scholarly journals Cks1 Activates Transcription by Binding to the Ubiquitylated Proteasome

2010 ◽  
Vol 30 (15) ◽  
pp. 3894-3901 ◽  
Author(s):  
Roman Holic ◽  
Alexander Kukalev ◽  
Sophie Lane ◽  
Edward J. Andress ◽  
Ivy Lau ◽  
...  
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Transcriptional Activation ◽  
Protein Complexes ◽  
Cyclin Dependent Kinase ◽  
Transcription Activator ◽  
Large Protein ◽  
Ubiquitin Binding ◽  
Ubiquitin Binding Domain ◽  
Proteasome Subunits

ABSTRACT Cyclin-dependent kinase-associated protein 1 (Cks1) is involved in the control of the transcription of a subset of genes in addition to its role in controlling the cell cycle in the budding yeast Saccharomyces cerevisiae. By directly ligating Cks1 onto a GAL1 promoter-driven reporter, we demonstrated that Cks1 acts as a transcription activator. Using this method, we dissected the downstream events from Cks1 recruitment at the promoter. We showed that subsequent to promoter binding, Cdc28 binding is required to modulate the level of gene expression. The ubiquitin-binding domain of Cks1 is essential for implementing downstream transcription events, which appears to recruit the proteasome via ubiquitylated proteasome subunits. We propose that the selective ability of Cks1 to bind ubiquitin allows this small molecule the flexibility to bind large protein complexes with specificity and that this may represent a novel mechanism of regulating transcriptional activation.

scholarly journals Negative feedback circuit for toll like receptor-8 activation in human embryonic Kidney 293 using outer membrane vesicle delivered bi-specific siRNA

2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Anurag Adhikari ◽  
Birendra Prasad Gupta ◽  
Krishna Das Manandhar ◽  
Shravan Kumar Mishra ◽  
Hari Krishna Saiju ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Negative Feedback ◽  
Membrane Vesicle ◽  
Outer Membrane Vesicle ◽  
Feedback Circuit ◽  
Toll Like Receptor ◽  
Human Embryonic Kidney ◽  
Negative Feedback Circuit
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