Heat Shock Partially Dissociates the Overlapping Modules of the Yeast Protein-Protein Interaction Network: A Systems Level Model of Adaptation

Mihalik, Ágoston; Csermely, Péter

doi:10.1371/journal.pcbi.1002187

Cited by 54 publications

(75 citation statements)

References 68 publications

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“…At the network level, Mihalik and Csermely analysed the effects of heat shock on the organization of the yeast interactome revealing partial disintegration of the interactome in response to this stress 120 . In the absence of global protein-protein interaction datasets generated under heat shock conditions, these authors exploited transcriptomic datasets to show that during heat shock there is a substantial decrease in the degree of overlap and the frequency of connections between the modules of the yeast interactome.…”

Section: Hsp90 Circuitry -Dynamic Behavioursmentioning

confidence: 99%

Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs

et al. 2012

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Preface Hsp90 is an essential, abundant, and ubiquitous eukaryotic chaperone that has crucial roles in protein folding and modulates the activities of key regulators. The fungal Hsp90 interactome, which includes numerous client proteins such as receptors, protein kinases and transcription factors, displays a surprisingly high degree of plasticity that depends on environmental conditions. Furthermore, although Hsp90 levels increase following environmental challenges, Hsp90 activity is tightly controlled via post-translational regulation and an autoregulatory loop involving the heat shock transcription factor, Hsf1. In this review, we discuss the roles and regulation of Hsp90. We propose that Hsp90 acts as a biological transistor that modulates the activity of fungal signalling networks in response to environmental cues via this Hsf1-Hsp90 autoregulatory loop.

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Section: Hsp90 Circuitry -Dynamic Behavioursmentioning

confidence: 99%

Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs

et al. 2012

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“…On the contrary, synthesis of HSP chaperones is grossly activated after stress [53]. Very interestingly, these major changes were recovered, when the protein-protein interaction network of stressed yeast cells was analyzed [54]. However, the two yeast chaperone sub-networks are not entirely distinct.…”

Section: Chaperone Networkmentioning

confidence: 98%

“…On top of all these, chaperone-mediated changes of far inter-modular contacts encode the integration of the environmental and intrinsic changes observed by the cell. The key multi-modular position gives molecular chaperones a special regulatory role, since they can easily couple, uncouple or even quarantine network communities, i.e., protein complexes, cellular organelles, such as damaged mitochondria, signaling pathways, metabolic routes or genetic regulatory circuits [22,24,48,54,79].…”

Section: Position and Dynamics Of Molecular Chaperones In Protein-promentioning

confidence: 99%

“…De-coupling of network modules may be so extensive that the damaged module becomes quarantined. Since decoupling efficiently prevents the propagation of network damage at the modular boundaries, chaperone-induced module de-coupling provides an additional safety measure for the cell [22,24,54,78,79].…”

Section: Short-term Adaptive Changes Of Cellular Network: Changes Ofmentioning

confidence: 99%

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System Level Mechanisms of Adaptation, Learning, Memory Formation and Evolvability: The Role of Chaperone and Other Networks

Gyurko

Sőti

Steták

et al. 2014

CPPS

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During the last decade, network approaches became a powerful tool to describe protein structure and dynamics. Here, we describe first the protein structure networks of molecular chaperones, then characterize chaperone containing sub-networks of interactomes called as chaperone-networks or chaperomes. We review the role of molecular chaperones in short-term adaptation of cellular networks in response to stress, and in long-term adaptation discussing their putative functions in the regulation of evolvability. We provide a general overview of possible network mechanisms of adaptation, learning and memory formation. We propose that changes of network rigidity play a key role in learning and memory formation processes. Flexible network topology provides 'learningcompetent' state. Here, networks may have much less modular boundaries than locally rigid, highly modular networks, where the learnt information has already been consolidated in a memory formation process. Since modular boundaries are efficient filters of information, in the 'learning-competent' state information filtering may be much smaller, than after memory formation. This mechanism restricts high information transfer to the 'learning competent' state. After memory formation, modular boundary-induced segregation and information filtering protect the stored information. The flexible networks of young organisms are generally in a 'learning competent' state. On the contrary, locally rigid networks of old organisms have lost their 'learning competent' state, but store and protect their learnt information efficiently. We anticipate that the above mechanism may operate at the level of both protein-protein interaction and neuronal networks.

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“…Such a stimulus, stressor or signal delivered to an already-diseased organism perturbs or disrupts ongoing disease dynamics and functional network organization of the system [68,69]. The disruption leads to transient wider fluctuations of bidirectional change for a period of time prior to re-stabilization [70][71][72] (Figure 1). Shaping the overall direction of the dynamics of change toward lasting health is the process and goal of treatment.…”

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confidence: 99%

Nonlinear Response Amplification Mechanisms for Low Doses of Natural Product Nanomedicines: Dynamical Interactions with the Recipient Complex Adaptive System

Bell

Sarter

Koithan

et al. 2013

J Nanomed Nanotechol

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The purpose of the present paper is (a) to outline the self-organized, complex adaptive network nature of the organism as recipient of nanomedicines; (b) to propose several nonlinear endogenous amplification processes by which pulsed low doses of traditional, homeopathically-manufactured natural product nanomedicines may stimulate a return toward healthier function; and (c) to discuss their potential relevance to novel, but safer than conventional dosing strategies for contemporary nanomedicines. Homeopathy is an over 200-year-old system of complementary and alternative medicine (CAM) that uses low doses of natural plant-, mineral-, and animal-sourced nanomedicines. Homeopathic manufacturing is "green", with mechanical grinding in lactose and agitation in ethanol-water as primary reagents. Agitation within glass containers at room temperature may also contribute nanosilica and nanosilicon as drug delivery vehicles and biological amplifiers. The medicine selection is matched to the recipient organism's systemic patterns of dysfunction and pulsed in the timing of the discrete doses. Endogenous amplification processes within the recipient organism may involve hormesis, time-dependent sensitization, and/or stochastic resonance. Effects are adaptive and systemically diffuse, i.e., causally indirect, rather than pharmacological and local, i.e., direct. All of these nonlinear response processes require interaction of the nanoparticle (NP) dose with the organism as a complex adaptive system. The pulsed NP dose serves as a low intensity salient danger signal for the organism to make network-wide adaptive changes that can lead to healing. The historically safe therapeutic approach of homeopathic nanomedicine dosing avoids risks of high, continuous doses and cumulative toxicity that contemporary nanomedicine researchers are now trying to solve while using NPs as if they were conventional bulk drugs. Integrating the insights, technical procedures, and clinical dosing approaches from modern and homeopathic nanomedicine could lead to major advances in the field for more effective and safer translational applications.NPs in homeopathic medicines [3]. NP concentrations are low, but measurable [3]. Like modern manufactured NPs [13], homeopathicallymanufactured medicines in solution also can exhibit aging effects [9,14]. These nanomedicines are delivered either in ethanolic liquids or sprayed and dried onto lactose or lactose/sucrose pellets for oral administration.Homeopathic manufacturing materials and methods are inherently "green" [15,16]. Previous papers have addressed the striking similarities between modern top-down mechanical attrition procedures for making nanoparticles (NPs) [17] and historical homeopathic medicine manufacturing methods and materials [15,[18][19][20][21]. These similarities include mechanically grinding source materials in lactose for hours and repeatedly agitating ethanol-water solutions containing the source Citation: Bell IR, Sarter B, Koithan M, Standish LJ, Banerji P, et al. (2013) Nonlinea...

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Heat Shock Partially Dissociates the Overlapping Modules of the Yeast Protein-Protein Interaction Network: A Systems Level Model of Adaptation

Cited by 54 publications

References 68 publications

Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs

Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs

System Level Mechanisms of Adaptation, Learning, Memory Formation and Evolvability: The Role of Chaperone and Other Networks

Nonlinear Response Amplification Mechanisms for Low Doses of Natural Product Nanomedicines: Dynamical Interactions with the Recipient Complex Adaptive System

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