Articles

  • Article |

    Nitrile-oxide electrophiles were identified as covalent inhibitors of GPX4 that exhibit increased selectivity and reduced off-target effects relative to chloroacetamide-based inhibitors.

    • John K. Eaton
    • , Laura Furst
    • , Richard A. Ruberto
    • , Dieter Moosmayer
    • , André Hilpmann
    • , Matthew J. Ryan
    • , Katja Zimmermann
    • , Luke L. Cai
    • , Michael Niehues
    • , Volker Badock
    • , Anneke Kramm
    • , Sixun Chen
    • , Roman C. Hillig
    • , Paul A. Clemons
    • , Stefan Gradl
    • , Claire Montagnon
    • , Kiel E. Lazarski
    • , Sven Christian
    • , Besnik Bajrami
    • , Roland Neuhaus
    • , Ashley L. Eheim
    • , Vasanthi S. Viswanathan
    •  & Stuart L. Schreiber
  • Article |

    The authors develop a ribozyme, Tx2.1, that is capable of aminoacylating tRNA with specificity for the anticodon from directed evolution of a T-box riboswitch. Tx2.1 could be used to charge non-natural amino acids in an in vitro translation system.

    • Satoshi Ishida
    • , Naohiro Terasaka
    • , Takayuki Katoh
    •  & Hiroaki Suga
  • Article |

    d-Cycloserine inactivates alanine racemase by forming an adduct with the pyridoxal 5′-phosphate cofactor, but structural and spectroscopic analyses reveal that reactivation occurs on adduct hydrolysis and product rearrangement to a stable oxime.

    • Cesira de Chiara
    • , Miha Homšak
    • , Gareth A. Prosser
    • , Holly L. Douglas
    • , Acely Garza-Garcia
    • , Geoff Kelly
    • , Andrew G. Purkiss
    • , Edward W. Tate
    •  & Luiz Pedro S. de Carvalho
  • Article |

    A structural study of one of two human phospholipase D enzymes, hPLD1, helps define the determinants of substrate recognition, the highly regulated enzymatic activity, as well as activation by PIP2 and RhoA.

    • Forrest Z. Bowling
    • , Christian M. Salazar
    • , Justin A. Bell
    • , Tahrima S. Huq
    • , Michael A. Frohman
    •  & Michael V. Airola
  • Article |

    A cryo-EM structure of potato virus X shows that virions are formed by repeats of segments of coat protein protomers arranged in a left-handed helical structure and reveals details of the RNA–capsid interactions, which shed light on virus assembly.

    • Alessandro Grinzato
    • , Eaazhisai Kandiah
    • , Chiara Lico
    • , Camilla Betti
    • , Selene Baschieri
    •  & Giuseppe Zanotti
  • Article |

    A cryo-EM structure of the GPCR α2B adrenergic receptor (α2BAR) in complex with the selective agonist dexmedetomidine and the G protein Go suggests a mechanism of selective activation and provides insights into G-protein coupling activity.

    • Daopeng Yuan
    • , Zhongmin Liu
    • , Jonas Kaindl
    • , Shoji Maeda
    • , Jiawei Zhao
    • , Xiaoou Sun
    • , Jun Xu
    • , Peter Gmeiner
    • , Hong-Wei Wang
    •  & Brian K. Kobilka
  • Article |

    Engineering of a synthetic circuit that couples transcriptional and protein turnover regulation to a fluorescent protein readout enables sensitive monitoring and amplification of gene expression signals from the unfolded protein response pathway.

    • Carlos A. Origel Marmolejo
    • , Bhagyashree Bachhav
    • , Sahiti D. Patibandla
    • , Alexander L. Yang
    •  & Laura Segatori
  • Article |

    Deep mutational scanning reveals that α-synuclein adopts a membrane-bound α-helix conformation with increasing dynamics towards the C terminus. This helical conformation is associated with its cytotoxicity.

    • Robert W. Newberry
    • , Jaime T. Leong
    • , Eric D. Chow
    • , Martin Kampmann
    •  & William F. DeGrado
  • Article |

    A set of CRISPR–Cas9-based genetic screens in a haploid human cell line identifies more than 200 gene–drug associations involving solute carriers (SLCs), transporters important for the uptake and activity of cytotoxic drugs.

    • Enrico Girardi
    • , Adrián César-Razquin
    • , Sabrina Lindinger
    • , Konstantinos Papakostas
    • , Justyna Konecka
    • , Jennifer Hemmerich
    • , Stefanie Kickinger
    • , Felix Kartnig
    • , Bettina Gürtl
    • , Kristaps Klavins
    • , Vitaly Sedlyarov
    • , Alvaro Ingles-Prieto
    • , Giuseppe Fiume
    • , Anna Koren
    • , Charles-Hugues Lardeau
    • , Richard Kumaran Kandasamy
    • , Stefan Kubicek
    • , Gerhard F. Ecker
    •  & Giulio Superti-Furga
  • Article |

    A small-molecule ligand of the APC/C activator Cdc20, which prolongs mitosis in unperturbed cells, instead shortens mitosis when the spindle checkpoint is activated, producing an opposite effect in a different regulatory context.

    • Katherine V. Richeson
    • , Tatyana Bodrug
    • , Katharine L. Sackton
    • , Masaya Yamaguchi
    • , Joao A. Paulo
    • , Steven P. Gygi
    • , Brenda A. Schulman
    • , Nicholas G. Brown
    •  & Randall W. King
  • Article |

    Small-molecule inhibitors of HIV-1 membrane fusion and infectivity act by partially inserting into a hydrophobic binding pocket formed by the membrane-proximal external region of Env spikes, blocking conformational changes of Env required for fusion.

    • Tianshu Xiao
    • , Gary Frey
    • , Qingshan Fu
    • , Christy L. Lavine
    • , David A. Scott
    • , Michael S. Seaman
    • , James J. Chou
    •  & Bing Chen
  • Article |

    Structural characterization of WbbM, an enzyme involved in O2a-antigen biosynthesis in Klebsiella pneumoniae, reveals two unique active sites with galactopyranosyl- or galactofuranosyl-transferase activities for oligosaccharide polymerization.

    • Bradley R. Clarke
    • , Olga G. Ovchinnikova
    • , Ryan P. Sweeney
    • , Evelyn R. Kamski-Hennekam
    • , Russel Gitalis
    • , Evan Mallette
    • , Steven D. Kelly
    • , Todd L. Lowary
    • , Matthew S. Kimber
    •  & Chris Whitfield
  • Article |

    Tuning CRISPR–Cas9 nuclease specificity enables precision genome engineering. Identifying arginine residues along the bridge helix of SpCas9 that mediate Cas9 mismatch sensitivity enabled engineering of Cas9 with increased specificity in human cells.

    • Majda Bratovič
    • , Ines Fonfara
    • , Krzysztof Chylinski
    • , Eric J. C. Gálvez
    • , Timothy J. Sullivan
    • , Stefan Boerno
    • , Bernd Timmermann
    • , Michael Boettcher
    •  & Emmanuelle Charpentier
  • Article |

    HIDE probes were developed for long time-lapse imaging of endolysosomes and their dynamics at super-resolution. These probes enabled analyses of endosome motility in primary fibroblasts from patients with Niemann–Pick C with distinct mutations in NPC1.

    • Aarushi Gupta
    • , Felix Rivera-Molina
    • , Zhiqun Xi
    • , Derek Toomre
    •  & Alanna Schepartz
  • Article |

    A high-throughput small-molecule drug screening platform enabled the detection of compounds targeting the functional interactions of receptor tyrosine kinases and identifies four new EGFR triple-mutant inhibitors.

    • Punit Saraon
    • , Jamie Snider
    • , Yannis Kalaidzidis
    • , Leanne E. Wybenga-Groot
    • , Konstantin Weiss
    • , Ankit Rai
    • , Nikolina Radulovich
    • , Luka Drecun
    • , Nika Vučković
    • , Adriana Vučetić
    • , Victoria Wong
    • , Brigitte Thériault
    • , Nhu-An Pham
    • , Jin H. Park
    • , Alessandro Datti
    • , Jenny Wang
    • , Shivanthy Pathmanathan
    • , Farzaneh Aboualizadeh
    • , Anna Lyakisheva
    • , Zhong Yao
    • , Yuhui Wang
    • , Babu Joseph
    • , Ahmed Aman
    • , Michael F. Moran
    • , Michael Prakesch
    • , Gennady Poda
    • , Richard Marcellus
    • , David Uehling
    • , Miroslav Samaržija
    • , Marko Jakopović
    • , Ming-Sound Tsao
    • , Frances A. Shepherd
    • , Adrian Sacher
    • , Natasha Leighl
    • , Anna Akhmanova
    • , Rima Al-awar
    • , Marino Zerial
    •  & Igor Stagljar
  • Article |

    Use of receptor variants in knock-in mice to dissect phosphorylation-dependent signaling from G protein-dependent signaling mediated by acetylcholine receptor M1 mAChR defines the ability of receptor ligands to modulate anxiety and locomotion behaviors.

    • Sophie J. Bradley
    • , Colin Molloy
    • , Paulina Valuskova
    • , Louis Dwomoh
    • , Miriam Scarpa
    • , Mario Rossi
    • , Lisa Finlayson
    • , Kjell A. Svensson
    • , Eyassu Chernet
    • , Vanessa N. Barth
    • , Karolina Gherbi
    • , David A. Sykes
    • , Caroline A. Wilson
    • , Rajendra Mistry
    • , Patrick M. Sexton
    • , Arthur Christopoulos
    • , Adrian J. Mogg
    • , Elizabeth M. Rosethorne
    • , Shuzo Sakata
    • , R. A. John Challiss
    • , Lisa M. Broad
    •  & Andrew B. Tobin
  • Article |

    In place of the expected flavin-C4a-(hydro)peroxide intermediate, certain flavin monooxygenases such as RutA instead use a flavin-N5-peroxide intermediate as a catalytic nucleophile, enabling chemistry not accessible to canonical monooxygenases.

    • Arne Matthews
    • , Raspudin Saleem-Batcha
    • , Jacob N. Sanders
    • , Frederick Stull
    • , K. N. Houk
    •  & Robin Teufel
  • Article |

    The ER exit site component Sec16A was identified as the target of Retro-2, a small-molecule inhibitor of protein toxins and pathogens. Retro-2 treatment alters retrograde early/maturing endosomes-to-Golgi trafficking of Shiga toxin.

    • Alison Forrester
    • , Stefan J. Rathjen
    • , Maria Daniela Garcia-Castillo
    • , Collin Bachert
    • , Audrey Couhert
    • , Livia Tepshi
    • , Sylvain Pichard
    • , Jennifer Martinez
    • , Mathilde Munier
    • , Raphael Sierocki
    • , Henri-François Renard
    • , César Augusto Valades-Cruz
    • , Florent Dingli
    • , Damarys Loew
    • , Christophe Lamaze
    • , Jean-Christophe Cintrat
    • , Adam D. Linstedt
    • , Daniel Gillet
    • , Julien Barbier
    •  & Ludger Johannes
  • Article |

    Susceptibility to ferroptosis can be modulated by nitric oxide (NO) and NO synthase iNOS and through enrichment of activated M1 macrophages. NO inhibits the lipoxygenase 15-LOX that drives production of pro-ferroptotic lipids in macrophages.

    • Alexandr A. Kapralov
    • , Qin Yang
    • , Haider H. Dar
    • , Yulia Y. Tyurina
    • , Tamil S. Anthonymuthu
    • , Rina Kim
    • , Claudette M. St. Croix
    • , Karolina Mikulska-Ruminska
    • , Bing Liu
    • , Indira H. Shrivastava
    • , Vladimir A. Tyurin
    • , Hsiu-Chi Ting
    • , Yijen L. Wu
    • , Yuan Gao
    • , Galina V. Shurin
    • , Margarita A. Artyukhova
    • , Liubov A. Ponomareva
    • , Peter S. Timashev
    • , Rosario M. Domingues
    • , Detcho A. Stoyanovsky
    • , Joel S. Greenberger
    • , Rama K. Mallampalli
    • , Ivet Bahar
    • , Dmitry I. Gabrilovich
    • , Hülya Bayır
    •  & Valerian E. Kagan
  • Article |

    Using genome-wide CRISPR–Cas9-mediated suppressor screens, cytochrome P450 oxidoreductase was identified as a contributor to ferroptotic cell death by promoting phospholipid peroxidation in various cellular lineages.

    • Yilong Zou
    • , Haoxin Li
    • , Emily T. Graham
    • , Amy A. Deik
    • , John K. Eaton
    • , Wenyu Wang
    • , Gerardo Sandoval-Gomez
    • , Clary B. Clish
    • , John G. Doench
    •  & Stuart L. Schreiber
  • Article |

    Redesigning the central carbon metabolism of Escherichia coli with the reductive glycine pathway enables growth on the one-carbon compounds formate and CO2, and the addition of methanol dehydrogenase further enables growth on methanol and CO2.

    • Seohyoung Kim
    • , Steffen N. Lindner
    • , Selçuk Aslan
    • , Oren Yishai
    • , Sebastian Wenk
    • , Karin Schann
    •  & Arren Bar-Even
  • Article |

    Certain cyanobacteria use an alternative biotin biosynthetic pathway that replaces BioA with the dehydrogenase BioU, a suicide enzyme that catalyzes its reaction via conjugation to Lys124 and loses the amino group of this residue in the process.

    • Kei Sakaki
    • , Keita Ohishi
    • , Tetsu Shimizu
    • , Ikki Kobayashi
    • , Naoki Mori
    • , Kenichi Matsuda
    • , Takeo Tomita
    • , Hidenori Watanabe
    • , Kan Tanaka
    • , Tomohisa Kuzuyama
    •  & Makoto Nishiyama
  • Article |

    A covalent pan-inhibitor of bacterial bile salt hydrolases developed by adding a chenodeoxycholic acid moiety to the warhead is not bactericidal and is therefore useful for studying the effects of bile acids on host physiology.

    • Arijit A. Adhikari
    • , Tom C. M. Seegar
    • , Scott B. Ficarro
    • , Megan D. McCurry
    • , Deepti Ramachandran
    • , Lina Yao
    • , Snehal N. Chaudhari
    • , Sula Ndousse-Fetter
    • , Alexander S. Banks
    • , Jarrod A. Marto
    • , Stephen C. Blacklow
    •  & A. Sloan Devlin
  • Article |

    Crystal structures of phospholipase hPLD1 and hPLD2 catalytic domains and an analysis of the binding modes of dual and isoform-selective inhibitors define mechanisms of PLD regulation and catalytic activity.

    • Claire M. Metrick
    • , Emily A. Peterson
    • , Joseph C. Santoro
    • , Istvan J. Enyedy
    • , Paramasivam Murugan
    • , TeYu Chen
    • , Klaus Michelsen
    • , Michael Cullivan
    • , Kerri A. Spilker
    • , P. Rajesh Kumar
    • , Tricia L. May-Dracka
    •  & Jayanth V. Chodaparambil
  • Article |

    NMR structural analysis of an active state of the β2-adrenergic receptor defines a unique orientation for the intracellular half of TM6, responsible for G-protein binding, including an equilibrium among three conformations of a key microswitch.

    • Shunsuke Imai
    • , Tomoki Yokomizo
    • , Yutaka Kofuku
    • , Yutaro Shiraishi
    • , Takumi Ueda
    •  & Ichio Shimada
  • Article |

    X-ray crystallography, solution NMR and biochemical and cell-based analyses reveal a model where catalytically repressed receptor tyrosine kinases accomplish activation loop (A-loop) tyrosine transphosphorylation.

    • Lingfeng Chen
    • , William M. Marsiglia
    • , Huaibin Chen
    • , Joseph Katigbak
    • , Hediye Erdjument-Bromage
    • , David J. Kemble
    • , Lili Fu
    • , Jinghong Ma
    • , Gongqin Sun
    • , Yingkai Zhang
    • , Guang Liang
    • , Thomas A. Neubert
    • , Xiaokun Li
    • , Nathaniel J. Traaseth
    •  & Moosa Mohammadi
  • Article |

    A series of positive allosteric modulators of NMDA receptors that can increase agonist potency, increase channel-open probability, and slow receptor deactivation can also decrease single-channel conductance and decrease calcium permeability.

    • Riley E. Perszyk
    • , Sharon A. Swanger
    • , Chris Shelley
    • , Alpa Khatri
    • , Gabriela Fernandez-Cuervo
    • , Matthew P. Epplin
    • , Jing Zhang
    • , Phuong Le
    • , Pernille Bülow
    • , Ethel Garnier-Amblard
    • , Pavan Kumar Reddy Gangireddy
    • , Gary J. Bassell
    • , Hongjie Yuan
    • , David S. Menaldino
    • , Dennis C. Liotta
    • , Lanny S. Liebeskind
    •  & Stephen F. Traynelis
  • Article |

    Lasonolide A is hydrolyzed into a cytotoxic metabolite by a lipid droplet-associated orphan serine hydrolase, showing that lipid droplets can promote drug toxicity by both accumulating and metabolizing drugs in cells.

    • Ramin Dubey
    • , Craig E. Stivala
    • , Huy Quoc Nguyen
    • , Young-Hwa Goo
    • , Antoni Paul
    • , Jan E. Carette
    • , Barry M. Trost
    •  & Rajat Rohatgi
  • Article |

    The X325 protein family is highly similar to lytic polysaccharide monooxygenases (LPMOs) in regulation, structure and copper coordination by a histidine brace, yet lacks LPMO activity and suggests the evolution of an alternative function in fungi.

    • Aurore Labourel
    • , Kristian E. H. Frandsen
    • , Feng Zhang
    • , Nicolas Brouilly
    • , Sacha Grisel
    • , Mireille Haon
    • , Luisa Ciano
    • , David Ropartz
    • , Mathieu Fanuel
    • , Francis Martin
    • , David Navarro
    • , Marie-Noëlle Rosso
    • , Tobias Tandrup
    • , Bastien Bissaro
    • , Katja S. Johansen
    • , Anastasia Zerva
    • , Paul H. Walton
    • , Bernard Henrissat
    • , Leila Lo Leggio
    •  & Jean-Guy Berrin
  • Article |

    A chemoproteomics and protein engineering strategy to investigate metabolic activity of lipid kinases led to assignment of a key role for atypical C1 domains in directing fatty acyl specificity of diacylglycerol kinase function in live cells.

    • Timothy B. Ware
    • , Caroline E. Franks
    • , Mitchell E. Granade
    • , Mingxing Zhang
    • , Kee-Beom Kim
    • , Kwon-Sik Park
    • , Andreas Gahlmann
    • , Thurl E. Harris
    •  & Ku-Lung Hsu
  • Article |

    Polypeptide GalNAc-transferase T3 catalyzes the specific glycosylation of threonine-178 of fibroblast growth factor 23, and structural insights reveal a unique lectin-based mechanism of substrate recognition.

    • Matilde de las Rivas
    • , Earnest James Paul Daniel
    • , Yoshiki Narimatsu
    • , Ismael Compañón
    • , Kentaro Kato
    • , Pablo Hermosilla
    • , Aurélien Thureau
    • , Laura Ceballos-Laita
    • , Helena Coelho
    • , Pau Bernadó
    • , Filipa Marcelo
    • , Lars Hansen
    • , Ryota Maeda
    • , Anabel Lostao
    • , Francisco Corzana
    • , Henrik Clausen
    • , Thomas A. Gerken
    •  & Ramon Hurtado-Guerrero
  • Article |

    In cotton, a specialized glyoxalase I variant, SPG, has lost its glutathione-binding sites and organelle-targeting signal during its evolution to catalyze the aromatization of cyclic sesquiterpenes as part of the gossypol biosynthetic pathway.

    • Jin-Quan Huang
    • , Xin Fang
    • , Xiu Tian
    • , Ping Chen
    • , Jia-Ling Lin
    • , Xiao-Xiang Guo
    • , Jian-Xu Li
    • , Zhen Fan
    • , Wei-Meng Song
    • , Fang-Yan Chen
    • , Ruzha Ahati
    • , Ling-Jian Wang
    • , Qing Zhao
    • , Cathie Martin
    •  & Xiao-Ya Chen
  • Article |

    In the fungal pathogen Cryptococcus neoformans, Bim1 is a copper-binding lytic polysaccharide monooxygenase-like protein that participates in copper uptake in concert with the Ctr1 importer to drive virulence mechanisms during fungal meningitis.

    • Sarela Garcia-Santamarina
    • , Corinna Probst
    • , Richard A. Festa
    • , Chen Ding
    • , Aaron D. Smith
    • , Steven E. Conklin
    • , Søren Brander
    • , Lisa N. Kinch
    • , Nick V. Grishin
    • , Katherine J. Franz
    • , Pamela Riggs-Gelasco
    • , Leila Lo Leggio
    • , Katja Salomon Johansen
    •  & Dennis J. Thiele
  • Article |

    Designed heterotrimers of collagen I, locked in three possible chain registers, enable structural and functional characterization of each permutation, leading to identification of the AAB heterotrimer as the most active and therefore likely to occur biologically.

    • Abhishek A. Jalan
    • , Douglas Sammon
    • , Jeffrey D. Hartgerink
    • , Paul Brear
    • , Katherine Stott
    • , Samir W. Hamaia
    • , Emma J. Hunter
    • , Douglas R. Walker
    • , Birgit Leitinger
    •  & Richard W. Farndale
  • Article |

    A set of orthogonal coiled-coil peptide heterodimers were developed to enable control of protein localization as well as transcriptional regulation by enhancing effector recruitment to TALE and CRISPR–dCas9 systems in mammalian cells and in vivo.

    • Tina Lebar
    • , Duško Lainšček
    • , Estera Merljak
    • , Jana Aupič
    •  & Roman Jerala
  • Article |

    The authors utilize fluorescence-activated cell sorting coupled with next-generation sequencing, as well as dynamic modeling, to study the molecular mechanism underlying indole signaling and reveal different roles of the two ends of tnaC in coordinating transcription and translation.

    • Tianmin Wang
    • , Xiang Zheng
    • , Haonan Ji
    • , Ting-Liang Wang
    • , Xin-Hui Xing
    •  & Chong Zhang
  • Article |

    UBE2T adopts an allosteric activation mechanism to mediate site-specific ubiquitination of Fanconi anemia complex. Interaction with FANCL induces a cascade of conformational changes of UBE2T and leads to exposure of substrate-binding sites.

    • Viduth K. Chaugule
    • , Connor Arkinson
    • , Martin L. Rennie
    • , Outi Kämäräinen
    • , Rachel Toth
    •  & Helen Walden
  • Article |

    Single-molecule FRET technologies reveal the mechanism of sequence-specific translational inhibition induced by two antibiotics, chloramphenicol and linezolid, where aminoacyl-tRNA was repeatedly rejected from the A-site and failed to form a peptide bond.

    • Junhong Choi
    • , James Marks
    • , Jingji Zhang
    • , Dong-Hua Chen
    • , Jinfan Wang
    • , Nora Vázquez-Laslop
    • , Alexander S. Mankin
    •  & Joseph D. Puglisi
  • Article |

    A combinatorial engineering strategy encompassing pathway regulation, heterologous enzymes and subcellular trafficking enables repurposing of the phospholipid biosynthetic pathway in Saccharomyces cerevisiae for the production of oleoylethanolamide.

    • Yi Liu
    • , Quanli Liu
    • , Anastasia Krivoruchko
    • , Sakda Khoomrung
    •  & Jens Nielsen
  • Article |

    An improved workflow combining de novo transcriptome assembly and Ribo-seq validated by cellular antigen display is developed to maximize small peptide discovery, leading to identification of thousands of unannotated protein-coding smORFs.

    • Thomas F. Martinez
    • , Qian Chu
    • , Cynthia Donaldson
    • , Dan Tan
    • , Maxim N. Shokhirev
    •  & Alan Saghatelian
  • Article |

    PUS10 exhibits two different functions: one is to promote miRNA biogenesis in a catalytically independent manner; the other is to install pseudouridine modification in tRNAs in a catalytically dependent manner.

    • Jinghui Song
    • , Yuan Zhuang
    • , Chenxu Zhu
    • , Haowei Meng
    • , Bo Lu
    • , Bingteng Xie
    • , Jinying Peng
    • , Mo Li
    •  & Chengqi Yi
  • Article |

    The crystal and cryo-electron microscopy structure analysis of the DCAF15–DDB1–DDA1–indisulam–RBM39 complex revealed the detailed mechanism of action of indisulam-induced RBM39 degradation and defined an α-helical degron motif in RBM39.

    • Dirksen E. Bussiere
    • , Lili Xie
    • , Honnappa Srinivas
    • , Wei Shu
    • , Ashley Burke
    • , Celine Be
    • , Junping Zhao
    • , Adarsh Godbole
    • , Dan King
    • , Rajeshri G. Karki
    • , Viktor Hornak
    • , Fangmin Xu
    • , Jennifer Cobb
    • , Nathalie Carte
    • , Andreas O. Frank
    • , Alexandra Frommlet
    • , Patrick Graff
    • , Mark Knapp
    • , Aleem Fazal
    • , Barun Okram
    • , Songchun Jiang
    • , Pierre-Yves Michellys
    • , Rohan Beckwith
    • , Hans Voshol
    • , Christian Wiesmann
    • , Jonathan M. Solomon
    •  & Joshiawa Paulk
  • Article |

    A hydrophobic tagging method is used to develop a selective degrader for the chromatin regulator EZH2, which inhibits proliferation of triple-negative breast cancer cell lines in vitro and in vivo.

    • Anqi Ma
    • , Elias Stratikopoulos
    • , Kwang-Su Park
    • , Jieli Wei
    • , Tiphaine C. Martin
    • , Xiaobao Yang
    • , Megan Schwarz
    • , Violetta Leshchenko
    • , Alexander Rialdi
    • , Brandon Dale
    • , Alessandro Lagana
    • , Ernesto Guccione
    • , Samir Parekh
    • , Ramon Parsons
    •  & Jian Jin
  • Article |

    The RNA endonuclease CPSF3 was identified as the cellular efficacy target of the small molecule JTE-607, revealing pre-mRNA processing as a vulnerability in cancers such as Ewing’s sarcoma that are characterized by aberrant transcription.

    • Nathan T. Ross
    • , Felix Lohmann
    • , Seth Carbonneau
    • , Aleem Fazal
    • , Wilhelm A. Weihofen
    • , Scott Gleim
    • , Michael Salcius
    • , Frederic Sigoillot
    • , Martin Henault
    • , Sarah H. Carl
    • , Juan B. Rodríguez-Molina
    • , Howard R. Miller
    • , Scott M. Brittain
    • , Jason Murphy
    • , Mark Zambrowski
    • , Geoffrey Boynton
    • , Yuan Wang
    • , Aye Chen
    • , Gregory J. Molind
    • , Johannes H. Wilbertz
    • , Caroline G. Artus-Revel
    • , Min Jia
    • , Favour A. Akinjiyan
    • , Jonathan Turner
    • , Judith Knehr
    • , Walter Carbone
    • , Sven Schuierer
    • , John S. Reece-Hoyes
    • , Kevin Xie
    • , Chitra Saran
    • , Eric T. Williams
    • , Guglielmo Roma
    • , Matt Spencer
    • , Jeremy Jenkins
    • , Elizabeth L. George
    • , Jason R. Thomas
    • , Gregory Michaud
    • , Markus Schirle
    • , John Tallarico
    • , Lori A. Passmore
    • , Jeffrey A. Chao
    •  & Rohan E. J. Beckwith
  • Article |

    Single-particle tracking and mathematical modeling methods reveal the searching mechanism of CTCF for its cognate sites on DNA. An RNA-binding region in CTCF mediates its trapping in small zones and increases its target search efficiency.

    • Anders S. Hansen
    • , Assaf Amitai
    • , Claudia Cattoglio
    • , Robert Tjian
    •  & Xavier Darzacq