Allosteric cross-talk in chromatin can mediate drug-drug synergy.

Abstract:

:Exploitation of drug-drug synergism and allostery could yield superior therapies by capitalizing on the immensely diverse, but highly specific, potential associated with the biological macromolecular landscape. Here we describe a drug-drug synergy mediated by allosteric cross-talk in chromatin, whereby the binding of one drug alters the activity of the second. We found two unrelated drugs, RAPTA-T and auranofin, that yield a synergistic activity in killing cancer cells, which coincides with a substantially greater number of chromatin adducts formed by one of the compounds when adducts from the other agent are also present. We show that this occurs through an allosteric mechanism within the nucleosome, whereby defined histone adducts of one drug promote reaction of the other drug at a distant, specific histone site. This opens up possibilities for epigenetic targeting and suggests that allosteric modulation in nucleosomes may have biological relevance and potential for therapeutic interventions.

journal_name

Nat Commun

journal_title

Nature communications

authors

Adhireksan Z,Palermo G,Riedel T,Ma Z,Muhammad R,Rothlisberger U,Dyson PJ,Davey CA

doi

10.1038/ncomms14860

subject

Has Abstract

pub_date

2017-03-30 00:00:00

pages

14860

issn

2041-1723

pii

ncomms14860

journal_volume

8

pub_type

杂志文章
  • Active and dynamic mitochondrial S-depalmitoylation revealed by targeted fluorescent probes.

    abstract::The reversible modification of cysteine residues by thioester formation with palmitate (S-palmitoylation) is an abundant lipid post-translational modification (PTM) in mammalian systems. S-palmitoylation has been observed on mitochondrial proteins, providing an intriguing potential connection between metabolic lipids ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-02655-1

    authors: Kathayat RS,Cao Y,Elvira PD,Sandoz PA,Zaballa ME,Springer MZ,Drake LE,Macleod KF,van der Goot FG,Dickinson BC

    更新日期:2018-01-23 00:00:00

  • Blunted ventral striatal responses to anticipated rewards foreshadow problematic drug use in novelty-seeking adolescents.

    abstract::Novelty-seeking tendencies in adolescents may promote innovation as well as problematic impulsive behaviour, including drug abuse. Previous research has not clarified whether neural hyper- or hypo-responsiveness to anticipated rewards promotes vulnerability in these individuals. Here we use a longitudinal design to tr...

    journal_title:Nature communications

    pub_type: 杂志文章,多中心研究

    doi:10.1038/ncomms14140

    authors: Büchel C,Peters J,Banaschewski T,Bokde AL,Bromberg U,Conrod PJ,Flor H,Papadopoulos D,Garavan H,Gowland P,Heinz A,Walter H,Ittermann B,Mann K,Martinot JL,Paillère-Martinot ML,Nees F,Paus T,Pausova Z,Poustka L,Riets

    更新日期:2017-02-21 00:00:00

  • Towards a new approach to reveal dynamical organization of the brain using topological data analysis.

    abstract::Little is known about how our brains dynamically adapt for efficient functioning. Most previous work has focused on analyzing changes in co-fluctuations between a set of brain regions over several temporal segments of the data. We argue that by collapsing data in space or time, we stand to lose useful information abou...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-03664-4

    authors: Saggar M,Sporns O,Gonzalez-Castillo J,Bandettini PA,Carlsson G,Glover G,Reiss AL

    更新日期:2018-04-11 00:00:00

  • Rapid, deep and precise profiling of the plasma proteome with multi-nanoparticle protein corona.

    abstract::Large-scale, unbiased proteomics studies are constrained by the complexity of the plasma proteome. Here we report a highly parallel protein quantitation platform integrating nanoparticle (NP) protein coronas with liquid chromatography-mass spectrometry for efficient proteomic profiling. A protein corona is a protein l...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-17033-7

    authors: Blume JE,Manning WC,Troiano G,Hornburg D,Figa M,Hesterberg L,Platt TL,Zhao X,Cuaresma RA,Everley PA,Ko M,Liou H,Mahoney M,Ferdosi S,Elgierari EM,Stolarczyk C,Tangeysh B,Xia H,Benz R,Siddiqui A,Carr SA,Ma P,Lan

    更新日期:2020-07-22 00:00:00

  • Fully-printed high-performance organic thin-film transistors and circuitry on one-micron-thick polymer films.

    abstract::Thin, ultra-flexible devices that can be manufactured in a process that covers a large area will be essential to realizing low-cost, wearable electronic applications including foldable displays and medical sensors. The printing technology will be instrumental in fabricating these novel electronic devices and circuits;...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms5147

    authors: Fukuda K,Takeda Y,Yoshimura Y,Shiwaku R,Tran LT,Sekine T,Mizukami M,Kumaki D,Tokito S

    更新日期:2014-06-20 00:00:00

  • Rotating-frame relaxation as a noise spectrum analyser of a superconducting qubit undergoing driven evolution.

    abstract::Gate operations in a quantum information processor are generally realized by tailoring specific periods of free and driven evolution of a quantum system. Unwanted environmental noise, which may in principle be distinct during these two periods, acts to decohere the system and increase the gate error rate. Although the...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms3337

    authors: Yan F,Gustavsson S,Bylander J,Jin X,Yoshihara F,Cory DG,Nakamura Y,Orlando TP,Oliver WD

    更新日期:2013-01-01 00:00:00

  • Asymmetric construction of tetrahedral chiral zinc with high configurational stability and catalytic activity.

    abstract::Chiral metal complexes show promise as asymmetric catalysts and optical materials. Chiral-at-metal complexes composed of achiral ligands have expanded the versatility and applicability of chiral metal complexes, especially for octahedral and half-sandwich complexes. However, Werner-type tetrahedral complexes with a st...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-20074-7

    authors: Endo K,Liu Y,Ube H,Nagata K,Shionoya M

    更新日期:2020-12-09 00:00:00

  • A cocktail of three virulent bacteriophages prevents Vibrio cholerae infection in animal models.

    abstract::Effective prevention strategies will be essential in reducing disease burden due to bacterial infections. Here we harness the specificity and rapid-acting properties of bacteriophages as a potential prophylaxis therapy for cholera, a severely dehydrating disease caused by Vibrio cholerae. To this end, we test a cockta...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms14187

    authors: Yen M,Cairns LS,Camilli A

    更新日期:2017-02-01 00:00:00

  • Controllable fatigue cracking mechanisms of copper bicrystals with a coherent twin boundary.

    abstract::High-angle grain boundaries are always the preferential fatigue cracking sites, while the intrinsic fatigue cracking mechanism of coherent twin boundary remains elusive. Here we systematically investigate the fatigue cracking behaviours of copper bicrystals with a coherent twin boundary as their sole internal boundary...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms4536

    authors: Li LL,Zhang ZJ,Zhang P,Wang ZG,Zhang ZF

    更新日期:2014-03-26 00:00:00

  • High-fidelity spin and optical control of single silicon-vacancy centres in silicon carbide.

    abstract::Scalable quantum networking requires quantum systems with quantum processing capabilities. Solid state spin systems with reliable spin-optical interfaces are a leading hardware in this regard. However, available systems suffer from large electron-phonon interaction or fast spin dephasing. Here, we demonstrate that the...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-09873-9

    authors: Nagy R,Niethammer M,Widmann M,Chen YC,Udvarhelyi P,Bonato C,Hassan JU,Karhu R,Ivanov IG,Son NT,Maze JR,Ohshima T,Soykal ÖO,Gali Á,Lee SY,Kaiser F,Wrachtrup J

    更新日期:2019-04-26 00:00:00

  • Ultra-low-frequency wave-driven diffusion of radiation belt relativistic electrons.

    abstract::Van Allen radiation belts are typically two zones of energetic particles encircling the Earth separated by the slot region. How the outer radiation belt electrons are accelerated to relativistic energies remains an unanswered question. Recent studies have presented compelling evidence for the local acceleration by ver...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms10096

    authors: Su Z,Zhu H,Xiao F,Zong QG,Zhou XZ,Zheng H,Wang Y,Wang S,Hao YX,Gao Z,He Z,Baker DN,Spence HE,Reeves GD,Blake JB,Wygant JR

    更新日期:2015-12-22 00:00:00

  • RNF115 plays dual roles in innate antiviral responses by catalyzing distinct ubiquitination of MAVS and MITA.

    abstract::MAVS and MITA are essential adaptor proteins mediating innate antiviral immune responses against RNA and DNA viruses, respectively. Here we show that RNF115 plays dual roles in response to RNA or DNA virus infections by catalyzing distinct types of ubiquitination of MAVS and MITA at different phases of viral infection...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-19318-3

    authors: Zhang ZD,Xiong TC,Yao SQ,Wei MC,Chen M,Lin D,Zhong B

    更新日期:2020-11-02 00:00:00

  • Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a substrate-specific cochaperone.

    abstract::Cytosolic HSP90 requires multiple cochaperones in folding client proteins. However, the function of gp96 (HSP90b1, grp94), an HSP90 paralogue in the endoplasmic reticulum (ER), is believed to be independent of cochaperones. Here, we demonstrate that gp96 chaperones multiple Toll-like receptors (TLRs), but not TLR3, in...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms1070

    authors: Liu B,Yang Y,Qiu Z,Staron M,Hong F,Li Y,Wu S,Li Y,Hao B,Bona R,Han D,Li Z

    更新日期:2010-09-21 00:00:00

  • Autophagy is a gatekeeper of hepatic differentiation and carcinogenesis by controlling the degradation of Yap.

    abstract::Activation of the Hippo pathway effector Yap underlies many liver cancers, however no germline or somatic mutations have been identified. Autophagy maintains essential metabolic functions of the liver, and autophagy-deficient murine models develop benign adenomas and hepatomegaly, which have been attributed to activat...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-07338-z

    authors: Lee YA,Noon LA,Akat KM,Ybanez MD,Lee TF,Berres ML,Fujiwara N,Goossens N,Chou HI,Parvin-Nejad FP,Khambu B,Kramer EGM,Gordon R,Pfleger C,Germain D,John GR,Campbell KN,Yue Z,Yin XM,Cuervo AM,Czaja MJ,Fiel MI,Hosh

    更新日期:2018-11-23 00:00:00

  • Assessment of corneal substrate biomechanics and its effect on epithelial stem cell maintenance and differentiation.

    abstract::Whilst demonstrated extensively in vitro, the control of cell behaviour via modulation of substrate compliance in live tissues has not been accomplished to date. Here we propose that stem cells can be regulated solely through in situ modulation of tissue biomechanics. By first establishing, via high-resolution Brillou...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-09331-6

    authors: Gouveia RM,Lepert G,Gupta S,Mohan RR,Paterson C,Connon CJ

    更新日期:2019-04-03 00:00:00

  • Tropomodulin3 is a novel Akt2 effector regulating insulin-stimulated GLUT4 exocytosis through cortical actin remodeling.

    abstract::Akt2 and its downstream effectors mediate insulin-stimulated GLUT4-storage vesicle (GSV) translocation and fusion with the plasma membrane (PM). Using mass spectrometry, we identify actin-capping protein Tropomodulin 3 (Tmod3) as an Akt2-interacting partner in 3T3-L1 adipocytes. We demonstrate that Tmod3 is phosphoryl...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms6951

    authors: Lim CY,Bi X,Wu D,Kim JB,Gunning PW,Hong W,Han W

    更新日期:2015-01-09 00:00:00

  • Global heat and salt transports by eddy movement.

    abstract::Oceanic mesoscale eddies contribute important horizontal heat and salt transports on a global scale. Here we show that eddy transports are mainly due to individual eddy movements. Theoretical and observational analyses indicate that cyclonic and anticyclonic eddies move westwards, and they also move polewards and equa...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms4294

    authors: Dong C,McWilliams JC,Liu Y,Chen D

    更新日期:2014-01-01 00:00:00

  • Shaping metallic glasses by electromagnetic pulsing.

    abstract::With damage tolerance rivalling advanced engineering alloys and thermoplastic forming capabilities analogous to conventional plastics, metallic glasses are emerging as a modern engineering material. Here, we take advantage of their unique electrical and rheological properties along with the classic Lorentz force conce...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms10576

    authors: Kaltenboeck G,Demetriou MD,Roberts S,Johnson WL

    更新日期:2016-02-08 00:00:00

  • A diverse intrinsic antibiotic resistome from a cave bacterium.

    abstract::Antibiotic resistance is ancient and widespread in environmental bacteria. These are therefore reservoirs of resistance elements and reflective of the natural history of antibiotics and resistance. In a previous study, we discovered that multi-drug resistance is common in bacteria isolated from Lechuguilla Cave, an un...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms13803

    authors: Pawlowski AC,Wang W,Koteva K,Barton HA,McArthur AG,Wright GD

    更新日期:2016-12-08 00:00:00

  • Impurity-band transport in organic spin valves.

    abstract::The central phenomenon in the field of organic spintronics is the large magnetoresistance in thick organic spin valves. A prerequisite for understanding the magnetoresistance is a reliable description of the device resistance, or the I-V characteristics. Here I show that the observed I-V characteristics in the organic...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms5842

    authors: Yu ZG

    更新日期:2014-09-09 00:00:00

  • Direct electrochemical oxidation of alcohols with hydrogen evolution in continuous-flow reactor.

    abstract::Alcohol oxidation reactions are widely used for the preparation of aldehydes and ketones. The electrolysis of alcohols to carbonyl compounds have been underutilized owing to low efficiency. Herein, we report an electrochemical oxidation of various alcohols in a continuous-flow reactor without external oxidants, base o...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-10928-0

    authors: Wang D,Wang P,Wang S,Chen YH,Zhang H,Lei A

    更新日期:2019-06-26 00:00:00

  • Multidomain architecture of estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains.

    abstract::Human estrogen receptor alpha (hERα) is a hormone-responsive nuclear receptor (NR) involved in cell growth and survival that contains both a DNA-binding domain (DBD) and a ligand-binding domain (LBD). Functionally relevant inter-domain interactions between the DBD and LBD have been observed in several other NRs, but f...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-06034-2

    authors: Huang W,Peng Y,Kiselar J,Zhao X,Albaqami A,Mendez D,Chen Y,Chakravarthy S,Gupta S,Ralston C,Kao HY,Chance MR,Yang S

    更新日期:2018-08-30 00:00:00

  • Soil bacterial diversity mediated by microscale aqueous-phase processes across biomes.

    abstract::Soil bacterial diversity varies across biomes with potential impacts on soil ecological functioning. Here, we incorporate key factors that affect soil bacterial abundance and diversity across spatial scales into a mechanistic modeling framework considering soil type, carbon inputs and climate towards predicting soil b...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-13966-w

    authors: Bickel S,Or D

    更新日期:2020-01-08 00:00:00

  • Josephson emission with frequency span 1-11 THz from small Bi2Sr2CaCu2O8+δ mesa structures.

    abstract::Mesa structures made of Bi2Sr2CaCu2O8+δ high-temperature superconductor represent stacks of atomic scale intrinsic Josephson junctions. They can be used for generation of high-frequency electromagnetic waves. Here we analyze Josephson emission from small-but-high mesas (with a small area, but containing many stacked j...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-01888-4

    authors: Borodianskyi EA,Krasnov VM

    更新日期:2017-11-23 00:00:00

  • Understanding catalysis in a multiphasic two-dimensional transition metal dichalcogenide.

    abstract::Establishing processing-structure-property relationships for monolayer materials is crucial for a range of applications spanning optics, catalysis, electronics and energy. Presently, for molybdenum disulfide, a promising catalyst for artificial photosynthesis, considerable debate surrounds the structure/property relat...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms9311

    authors: Chou SS,Sai N,Lu P,Coker EN,Liu S,Artyushkova K,Luk TS,Kaehr B,Brinker CJ

    更新日期:2015-10-07 00:00:00

  • Three-dimensional localization spectroscopy of individual nuclear spins with sub-Angstrom resolution.

    abstract::Nuclear magnetic resonance (NMR) spectroscopy is a powerful method for analyzing the chemical composition and molecular structure of materials. At the nanometer scale, NMR has the prospect of mapping the atomic-scale structure of individual molecules, provided a method that can sensitively detect single nuclei and mea...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-07121-0

    authors: Zopes J,Cujia KS,Sasaki K,Boss JM,Itoh KM,Degen CL

    更新日期:2018-11-08 00:00:00

  • Air-stable redox-active nanomagnets with lanthanide spins radical-bridged by a metal-metal bond.

    abstract::Engineering intramolecular exchange interactions between magnetic metal atoms is a ubiquitous strategy for designing molecular magnets. For lanthanides, the localized nature of 4f electrons usually results in weak exchange coupling. Mediating magnetic interactions between lanthanide ions via radical bridges is a fruit...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-08513-6

    authors: Liu F,Velkos G,Krylov DS,Spree L,Zalibera M,Ray R,Samoylova NA,Chen CH,Rosenkranz M,Schiemenz S,Ziegs F,Nenkov K,Kostanyan A,Greber T,Wolter AUB,Richter M,Büchner B,Avdoshenko SM,Popov AA

    更新日期:2019-02-04 00:00:00

  • Geographic population structure analysis of worldwide human populations infers their biogeographical origins.

    abstract::The search for a method that utilizes biological information to predict humans' place of origin has occupied scientists for millennia. Over the past four decades, scientists have employed genetic data in an effort to achieve this goal but with limited success. While biogeographical algorithms using next-generation seq...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms4513

    authors: Elhaik E,Tatarinova T,Chebotarev D,Piras IS,Maria Calò C,De Montis A,Atzori M,Marini M,Tofanelli S,Francalacci P,Pagani L,Tyler-Smith C,Xue Y,Cucca F,Schurr TG,Gaieski JB,Melendez C,Vilar MG,Owings AC,Gómez R,Fuji

    更新日期:2014-04-29 00:00:00

  • Interactions with conspecific outsiders as drivers of cognitive evolution.

    abstract::The social intelligence hypothesis (SIH) posits that within-group interactions drive cognitive evolution, but it has received equivocal support. We argue the SIH overlooks a major component of social life: interactions with conspecific outsiders. Competition for vital resources means conspecific outsiders present myri...

    journal_title:Nature communications

    pub_type: 杂志文章,评审

    doi:10.1038/s41467-020-18780-3

    authors: Ashton BJ,Kennedy P,Radford AN

    更新日期:2020-10-06 00:00:00

  • Direct measurement of individual phonon lifetimes in the clathrate compound Ba7.81Ge40.67Au5.33.

    abstract::Engineering lattice thermal conductivity requires to control the heat carried by atomic vibration waves, the phonons. The key parameter for quantifying it is the phonon lifetime, limiting the travelling distance, whose determination is however at the limits of instrumental capabilities. Here, we show the achievement o...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-00584-7

    authors: Lory PF,Pailhès S,Giordano VM,Euchner H,Nguyen HD,Ramlau R,Borrmann H,Schmidt M,Baitinger M,Ikeda M,Tomeš P,Mihalkovič M,Allio C,Johnson MR,Schober H,Sidis Y,Bourdarot F,Regnault LP,Ollivier J,Paschen S,Grin Y,d

    更新日期:2017-09-08 00:00:00