Cell biology

  • Article
    | Open Access

    The Lys48-linked polyubiquitin-mediated proteasomal degradation in yeast depends on Cdc48 and its cofactors Ufd1 and Npl4. Here, the authors present crystal structures of Npl4 bound to Lys48-linked diubiquitin and the Npl4-binding motif of Ufd1, providing insights into the reaction mechanism of the Cdc48- Ufd1/Npl4 complex.

    • Yusuke Sato
    • , Hikaru Tsuchiya
    • , Atsushi Yamagata
    • , Kei Okatsu
    • , Keiji Tanaka
    • , Yasushi Saeki
    •  & Shuya Fukai
  • Article
    | Open Access

    Rap1 is a telomeric protein that is highly expressed in cancers. Here, the authors show that Rap1 interacts with several DNA repair proteins independent of its telomere function to enhance DNA repair and that its deficiency leads to accelerated tumorigenesis, but enhanced sensitivity to genotoxic stress.

    • Ekta Khattar
    • , Kyaw Ze Ya Maung
    • , Chen Li Chew
    • , Arkasubhra Ghosh
    • , Michelle Meng Huang Mok
    • , Pei Lee
    • , Jun Zhang
    • , Wei Hong Jeff Chor
    • , Gökhan Cildir
    • , Chelsia Qiuxia Wang
    • , Nur Khairiah Mohd-Ismail
    • , Desmond Wai Loon Chin
    • , Soo Chin Lee
    • , Henry Yang
    • , Yong-Jae Shin
    • , Do-Hyun Nam
    • , Liming Chen
    • , Alan Prem Kumar
    • , Lih Wen Deng
    • , Masahito Ikawa
    • , Jayantha Gunaratne
    • , Motomi Osato
    •  & Vinay Tergaonkar
  • Article
    | Open Access

    The design of protein assemblies is a major thrust for biomolecular engineering and nanobiotechnology. Here the authors demonstrate a general mechanism for designing allosteric macromolecular assemblies and showcase a proof of concept for engineered allosteric protein assembly.

    • Luis A. Campos
    • , Rajendra Sharma
    • , Sara Alvira
    • , Federico M. Ruiz
    • , Beatriz Ibarra-Molero
    • , Mourad Sadqi
    • , Carlos Alfonso
    • , Germán Rivas
    • , Jose M. Sanchez-Ruiz
    • , Antonio Romero Garrido
    • , José M. Valpuesta
    •  & Victor Muñoz
  • Article
    | Open Access

    Common Fragile Sites (CFSs) are chromosome regions prone to breakage upon replication stress known to drive chromosome rearrangements during oncogenesis. Here the authors use genome-wide and single cell techniques to assess how replication timing and transcriptional activity correlate with genome stability.

    • Olivier Brison
    • , Sami El-Hilali
    • , Dana Azar
    • , Stéphane Koundrioukoff
    • , Mélanie Schmidt
    • , Viola Nähse
    • , Yan Jaszczyszyn
    • , Anne-Marie Lachages
    • , Bernard Dutrillaux
    • , Claude Thermes
    • , Michelle Debatisse
    •  & Chun-Long Chen
  • Article
    | Open Access

    Primary cilia have been proposed to regulate glucose metabolism and insulin secretion in beta cells, but it is not known how. Here the authors show that primary cilia play a role in adult β-cell function via a mechanism involving endosomal EphA-processing.

    • Francesco Volta
    • , M. Julia Scerbo
    • , Anett Seelig
    • , Robert Wagner
    • , Nils O’Brien
    • , Felicia Gerst
    • , Andreas Fritsche
    • , Hans-Ulrich Häring
    • , Anja Zeigerer
    • , Susanne Ullrich
    •  & Jantje M. Gerdes
  • Article
    | Open Access

    Cell senescence involves stable arrest of cell proliferation and changes in gene expression and 3D genome reorganization. Here, the authors show that human condensin II complex participates in reorganization of the chromatin compartments, primarily through switching from heterochromatic B to euchromatic A compartments.

    • Osamu Iwasaki
    • , Hideki Tanizawa
    • , Kyoung-Dong Kim
    • , Andrew Kossenkov
    • , Timothy Nacarelli
    • , Sanki Tashiro
    • , Sonali Majumdar
    • , Louise C. Showe
    • , Rugang Zhang
    •  & Ken-ichi Noma
  • Article
    | Open Access

    UVRAG is involved in autophagy, which loses its tumour suppressor functions when in its truncated form in cancers. Here, the authors use a mouse model that inducibly express this truncated protein and show impaired autophagy, enhanced inflammation and β-catenin stabilisation, which promotes spontaneous tumorigenesis.

    • Christine Quach
    • , Ying Song
    • , Hongrui Guo
    • , Shun Li
    • , Hadi Maazi
    • , Marshall Fung
    • , Nathaniel Sands
    • , Douglas O’Connell
    • , Sara Restrepo-Vassalli
    • , Billy Chai
    • , Dali Nemecio
    • , Vasu Punj
    • , Omid Akbari
    • , Gregory E. Idos
    • , Shannon M. Mumenthaler
    • , Nancy Wu
    • , Sue Ellen Martin
    • , Ashley Hagiya
    • , James Hicks
    • , Hengmin Cui
    •  & Chengyu Liang
  • Article
    | Open Access

    Phagocytosis is a typically eukaryotic feature that could be behind the origin of eukaryotic cells. Here, the authors describe a bacterium that can engulf other bacteria and small eukaryotic cells through a phagocytosis-like mechanism.

    • Takashi Shiratori
    • , Shigekatsu Suzuki
    • , Yukako Kakizawa
    •  & Ken-ichiro Ishida
  • Article
    | Open Access

    Single-molecule in vitro assays require dedicated confocal microscopes equipped with fluorescence correlation spectroscopy (FCS) modules. Here the authors present a compact, cheap and open-source 3D-printed confocal microscope for single photon counting and FCS measurements, and use it to detect α-synuclein aggregation.

    • James W. P. Brown
    • , Arnaud Bauer
    • , Mark E Polinkovsky
    • , Akshay Bhumkar
    • , Dominic J. B. Hunter
    • , Katharina Gaus
    • , Emma Sierecki
    •  & Yann Gambin
  • Article
    | Open Access

    Organoid cultures have been developed from multiple tissues, opening new possibilities for regenerative medicine. Here the authors demonstrate the derivation of GMP-compliant hydrogels from decellularized porcine small intestine which support formation and growth of human gastric, liver, pancreatic and small intestinal organoids.

    • Giovanni Giuseppe Giobbe
    • , Claire Crowley
    • , Camilla Luni
    • , Sara Campinoti
    • , Moustafa Khedr
    • , Kai Kretzschmar
    • , Martina Maria De Santis
    • , Elisa Zambaiti
    • , Federica Michielin
    • , Laween Meran
    • , Qianjiang Hu
    • , Gijs van Son
    • , Luca Urbani
    • , Anna Manfredi
    • , Monica Giomo
    • , Simon Eaton
    • , Davide Cacchiarelli
    • , Vivian S. W. Li
    • , Hans Clevers
    • , Paola Bonfanti
    • , Nicola Elvassore
    •  & Paolo De Coppi
  • Article
    | Open Access

    Most cases of autosomal dominant polycystic kidney disease (ADPKD) are due to mutations in PKD1. Here, Tsukiyama et al. generate monkeys with mutations in PKD1 and show that animals recapitulate key pathological features of the human disease, suggesting these may provide insights into ADPKD pathogenesis and contribute to the development of future therapeutic strategies.

    • Tomoyuki Tsukiyama
    • , Kenichi Kobayashi
    • , Masataka Nakaya
    • , Chizuru Iwatani
    • , Yasunari Seita
    • , Hideaki Tsuchiya
    • , Jun Matsushita
    • , Kahoru Kitajima
    • , Ikuo Kawamoto
    • , Takahiro Nakagawa
    • , Koji Fukuda
    • , Teppei Iwakiri
    • , Hiroyuki Izumi
    • , Iori Itagaki
    • , Shinji Kume
    • , Hiroshi Maegawa
    • , Ryuichi Nishinakamura
    • , Saori Nishio
    • , Shinichiro Nakamura
    • , Akihiro Kawauchi
    •  & Masatsugu Ema
  • Article
    | Open Access

    While the cellular recycling process autophagy has been linked to aging, the impact of selective autophagy on lifespan remains unclear. Here Kumsta et al. show that the autophagy receptor p62/SQSTM1 is required for hormetic benefits and p62/SQSTM1 overexpression is sufficient to extend C. elegans lifespan and improve proteostasis.

    • Caroline Kumsta
    • , Jessica T. Chang
    • , Reina Lee
    • , Ee Phie Tan
    • , Yongzhi Yang
    • , Rute Loureiro
    • , Elizabeth H. Choy
    • , Shaun H. Y. Lim
    • , Isabel Saez
    • , Alexander Springhorn
    • , Thorsten Hoppe
    • , David Vilchez
    •  & Malene Hansen
  • Article
    | Open Access

    PARG catalyzes the removal of poly(ADP-ribose) (PAR) from target proteins and executes critical functions in the DNA damage response. Here the authors provide structural and biological insight with small molecule PARG inhibitors and show that PARG inhibition sensitizes cells to ionizing radiation and kills cancer cells through replication fork defects.

    • Jerry H. Houl
    • , Zu Ye
    • , Chris A. Brosey
    • , Lakshitha P. F. Balapiti-Modarage
    • , Sarita Namjoshi
    • , Albino Bacolla
    • , Daniel Laverty
    • , Brian L. Walker
    • , Yasin Pourfarjam
    • , Leslie S. Warden
    • , Naga Babu Chinnam
    • , Davide Moiani
    • , Roderick A. Stegeman
    • , Mei-Kuang Chen
    • , Mien-Chie Hung
    • , Zachary D. Nagel
    • , Tom Ellenberger
    • , In-Kwon Kim
    • , Darin E. Jones
    • , Zamal Ahmed
    •  & John A. Tainer
  • Article
    | Open Access

    It was known that prolonged TRMPL1 activation induces TFEB translocation and upregulates autophagic gene regulation. Here, the authors show that acute TRMPL1 activation also induces autophagy through VPS34 and by lysosomal calcium release independent of TFEB.

    • A. Scotto Rosato
    • , S. Montefusco
    • , C. Soldati
    • , S. Di Paola
    • , A. Capuozzo
    • , J. Monfregola
    • , E. Polishchuk
    • , A. Amabile
    • , C. Grimm
    • , A. Lombardo
    • , M. A. De Matteis
    • , A. Ballabio
    •  & D. L. Medina
  • Article
    | Open Access

    During meiosis, pairing of homologous chromosomes is critical for sexual reproduction. Here the authors reveal in S. pombe the role of lncRNA–protein complexes during the pairing of homologues chromosomes that assemble at specific chromosomal loci to mediate recognition of the pairs.

    • Da-Qiao Ding
    • , Kasumi Okamasa
    • , Yuki Katou
    • , Eriko Oya
    • , Jun-ichi Nakayama
    • , Yuji Chikashige
    • , Katsuhiko Shirahige
    • , Tokuko Haraguchi
    •  & Yasushi Hiraoka
  • Article
    | Open Access

    Senescence of metabolically active cells is a process linked to ageing. Here the authors reveal that CSB is required to block replicative senescence, and epigenetic control of CSB downregulation triggers proliferative arrest in a p21-dependent manner.

    • Clément Crochemore
    • , Cristina Fernández-Molina
    • , Benjamin Montagne
    • , Audrey Salles
    •  & Miria Ricchetti
  • Article
    | Open Access

    Yamanaka factors can reprogram somatic and cancer cells into induced pluripotent stem cells. Here, the authors show that the induction of these factors in acute myeloid leukemia leads to apoptosis of leukemia cells in vivo, and this is through modulation of chromatin accessibility to apoptotic genes and accompanied by H3K9me3 dysregulation.

    • Yajie Wang
    • , Ting Lu
    • , Guohuan Sun
    • , Yawei Zheng
    • , Shangda Yang
    • , Hongyan Zhang
    • , Sha Hao
    • , Yanfeng Liu
    • , Shihui Ma
    • , Houyu Zhang
    • , Yongxin Ru
    • , Shaorong Gao
    • , Kuangyu Yen
    • , Hui Cheng
    •  & Tao Cheng
  • Article
    | Open Access

    SPOR domains are present in bacterial proteins that recognize cell-wall peptidoglycan strands stripped of the peptide stems. Here, Alcorlo et al. show that, indeed, the presence of peptide stems abrogates binding to a SPOR domain, and provide insights into the molecular basis for recognition.

    • Martín Alcorlo
    • , David A. Dik
    • , Stefania De Benedetti
    • , Kiran V. Mahasenan
    • , Mijoon Lee
    • , Teresa Domínguez-Gil
    • , Dusan Hesek
    • , Elena Lastochkin
    • , Daniel López
    • , Bill Boggess
    • , Shahriar Mobashery
    •  & Juan A. Hermoso
  • Article
    | Open Access

    The adult mammalian inner ear cells cannot regenerate nor proliferate. Here, the authors show that co-activation of Myc and NOTCH pathways can stimulate proliferation of inner ear sensory epithelial cells, which can be induced to become hair cell-like cells in vitro and in vivo.

    • Yilai Shu
    • , Wenyan Li
    • , Mingqian Huang
    • , Yi-Zhou Quan
    • , Deborah Scheffer
    • , Chunjie Tian
    • , Yong Tao
    • , Xuezhong Liu
    • , Konrad Hochedlinger
    • , Artur A. Indzhykulian
    • , Zhengmin Wang
    • , Huawei Li
    •  & Zheng-Yi Chen
  • Article
    | Open Access

    Brassinosteroid signaling can regulate auxin transport by influencing the sorting and accumulation of PIN auxin efflux carriers. Here, the authors show that in roots, brassinolide can modulate vacuolar degradation and endocytic sorting of PIN2, delimiting root curvature in response to gravity.

    • Katarzyna Retzer
    • , Maria Akhmanova
    • , Nataliia Konstantinova
    • , Kateřina Malínská
    • , Johannes Leitner
    • , Jan Petrášek
    •  & Christian Luschnig
  • Article
    | Open Access

    Thermal characterization of biological tissues can traditionally provide either large fields of view or high resolution. By the development of super-resolution infrared photo-thermal imaging, the authors reconstruct temperature-based maps of absorptive centers in millimeter-sized biological samples.

    • M. Bouzin
    • , M. Marini
    • , A. Zeynali
    • , M. Borzenkov
    • , L. Sironi
    • , L. D’Alfonso
    • , F. Mingozzi
    • , F. Granucci
    • , P. Pallavicini
    • , G. Chirico
    •  & M. Collini
  • Article
    | Open Access

    Mutation of the nuclear envelope protein, barrier-to-autointegration factor 1 (Banf1), has previously been associated with the development of ageing associated diseases in a human progeria syndrome. Here, the authors reveal the functional link between Banf1-regulated, PARP1-directed repair of oxidative lesions.

    • Emma Bolderson
    • , Joshua T. Burgess
    • , Jun Li
    • , Neha S. Gandhi
    • , Didier Boucher
    • , Laura V. Croft
    • , Samuel Beard
    • , Jennifer J. Plowman
    • , Amila Suraweera
    • , Mark N. Adams
    • , Ali Naqi
    • , Shu-Dong Zhang
    • , David A. Sinclair
    • , Kenneth J. O’Byrne
    •  & Derek J. Richard
  • Article
    | Open Access

    LRIG1 is a tumour suppressor in several cancers. Here, the authors show that androgen receptor directly transactivates LRIG1 which then antagonises ERBB signalling and c-Myc expression to inhibit prostate tumorigenesis.

    • Qiuhui Li
    • , Bigang Liu
    • , Hsueh-Ping Chao
    • , Yibing Ji
    • , Yue Lu
    • , Rashid Mehmood
    • , Collene Jeter
    • , Taiping Chen
    • , John R. Moore
    • , Wenqian Li
    • , Can Liu
    • , Kiera Rycaj
    • , Amanda Tracz
    • , Jason Kirk
    • , Tammy Calhoun-Davis
    • , Jie Xiong
    • , Qu Deng
    • , Jiaoti Huang
    • , Barbara A. Foster
    • , Abhiram Gokhale
    • , Xin Chen
    •  & Dean G. Tang
  • Article
    | Open Access

    Major effect loci controlling natural, heritable variation in telomere length are not known. Here, the authors use QTL mapping and transgenic manipulations in Arabidopsis to implicate the rRNA-processing genes NOP2A and RPL5 in telomere length set point regulation in this model species.

    • Liliia R. Abdulkina
    • , Callie Kobayashi
    • , John T. Lovell
    • , Inna B. Chastukhina
    • , Behailu B. Aklilu
    • , Inna A. Agabekian
    • , Ana V. Suescún
    • , Lia R. Valeeva
    • , Chuluuntsetseg Nyamsuren
    • , Galina V. Aglyamova
    • , Margarita R. Sharipova
    • , Dorothy E. Shippen
    • , Thomas E. Juenger
    •  & Eugene V. Shakirov
  • Article
    | Open Access

    The activation mechanism of integrin αVβ8 differs from other integrins. Combining X-ray crystallography, hydrogen deuterium exchange mass spectrometry and mutation, the authors reveal structural features responsible for these differences and provide insights into how typical integrins are regulated.

    • Jianchuan Wang
    • , Yang Su
    • , Roxana E. Iacob
    • , John R. Engen
    •  & Timothy A. Springer
  • Article
    | Open Access

    Pre-malignant cells harbouring oncogenic mutations can populate and spread throughout a tissue. Here, using a rainbow mouse system, the authors explore how clonal expansion in the mouse intestine might explain high levels of intra-tumoural heterogeneity observed in the disease.

    • Peter G. Boone
    • , Lauren K. Rochelle
    • , Joshua D. Ginzel
    • , Veronica Lubkov
    • , Wendy L. Roberts
    • , P. J. Nicholls
    • , Cheryl Bock
    • , Mei Lang Flowers
    • , Richard J. von Furstenberg
    • , Barry R. Stripp
    • , Pankaj Agarwal
    • , Alexander D. Borowsky
    • , Robert D. Cardiff
    • , Larry S. Barak
    • , Marc G. Caron
    • , H. Kim Lyerly
    •  & Joshua C. Snyder
  • Article
    | Open Access

    Gemcitabine is used to treat gallbaldder cancer but patient responses are variable. Here, the authors use a genome-wide CRISPR screen and identify the translational elongator protein ELP5 as a protein that is important for mediating gemcitabine-induced apoptosis.

    • Sunwang Xu
    • , Ming Zhan
    • , Cen Jiang
    • , Min He
    • , Linhua Yang
    • , Hui Shen
    • , Shuai Huang
    • , Xince Huang
    • , Ruirong Lin
    • , Yongheng Shi
    • , Qiang Liu
    • , Wei Chen
    • , Man Mohan
    •  & Jian Wang
  • Article
    | Open Access

    Crosstalk between protein oxidation and other post-translational modifications remains unexplored. Here, the authors map the phosphoproteome, cysteine redox proteome and total proteome of adipocytes under acute oxidative stress and reveal crosstalk between cysteine oxidation and phosphorylation-based signalling.

    • Zhiduan Su
    • , James G. Burchfield
    • , Pengyi Yang
    • , Sean J. Humphrey
    • , Guang Yang
    • , Deanne Francis
    • , Sabina Yasmin
    • , Sung-Young Shin
    • , Dougall M. Norris
    • , Alison L. Kearney
    • , Miro A. Astore
    • , Jonathan Scavuzzo
    • , Kelsey H. Fisher-Wellman
    • , Qiao-Ping Wang
    • , Benjamin L. Parker
    • , G. Gregory Neely
    • , Fatemeh Vafaee
    • , Joyce Chiu
    • , Reichelle Yeo
    • , Philip J. Hogg
    • , Daniel J. Fazakerley
    • , Lan K. Nguyen
    • , Serdar Kuyucak
    •  & David E. James
  • Article
    | Open Access

    One of the underlying causes of aging is the accumulation of senescent cells, but their turnover rates and dynamics during ageing are unknown. Here the authors measure and model senescent cell production and removal and explore implications for mortality.

    • Omer Karin
    • , Amit Agrawal
    • , Ziv Porat
    • , Valery Krizhanovsky
    •  & Uri Alon
  • Article
    | Open Access

    Inducible genome editing systems often suffer from leakiness or reduced activity. Here the authors develop CRISPR-Switch, a Cre recombinase ON/OFF-controlled sgRNA cassette that allows consecutive editing of two loci.

    • Krzysztof Chylinski
    • , Maria Hubmann
    • , Ruth E. Hanna
    • , Connor Yanchus
    • , Georg Michlits
    • , Esther C. H. Uijttewaal
    • , John Doench
    • , Daniel Schramek
    •  & Ulrich Elling
  • Article
    | Open Access

    There is growing evidence that autophagy might serve specialized functions in neurons besides its role in protein homeostasis. In this study, authors demonstrate that axonal retrograde transport of BDNF/TrkB in neuronal amphisomes is involved in plasticity-relevant local signaling at presynaptic boutons and that SIPA1L2, a member of the SIPA1L family of neuronal RapGAPs, associates via LC3b to TrkB-containing amphisomes to regulate its motility and signaling at the axon terminals

    • Maria Andres-Alonso
    • , Mohamed Raafet Ammar
    • , Ioana Butnaru
    • , Guilherme M. Gomes
    • , Gustavo Acuña Sanhueza
    • , Rajeev Raman
    • , PingAn Yuanxiang
    • , Maximilian Borgmeyer
    • , Jeffrey Lopez-Rojas
    • , Syed Ahsan Raza
    • , Nicola Brice
    • , Torben J. Hausrat
    • , Tamar Macharadze
    • , Silvia Diaz-Gonzalez
    • , Mark Carlton
    • , Antonio Virgilio Failla
    • , Oliver Stork
    • , Michaela Schweizer
    • , Eckart D. Gundelfinger
    • , Matthias Kneussel
    • , Christina Spilker
    • , Anna Karpova
    •  & Michael R. Kreutz
  • Article
    | Open Access

    DNA ligases catalyze the joining of DNA strands to complete DNA replication, recombination and repair transactions. Here the authors present X-ray structures and kinetic analyses of LIG1 complexes with undamaged and oxidatively damaged DNA that unveil determinants of LIG1 substrate recognition and enzymatic fidelity.

    • Percy P. Tumbale
    • , Thomas J. Jurkiw
    • , Matthew J. Schellenberg
    • , Amanda A. Riccio
    • , Patrick J O’Brien
    •  & R. Scott Williams
  • Article
    | Open Access

    The human ATP-binding cassette transporter ABCG2 plays critical roles in anticancer resistance but the molecular mechanism of ABCG2-mediated substrate transport remains enigmatic. Here authors use extensive mutagenesis and molecular dynamics simulations to reveal a mechanistic basis for the function of the di-leucine valve and the roof organization in the transport cycle.

    • Narakorn Khunweeraphong
    • , Daniel Szöllősi
    • , Thomas Stockner
    •  & Karl Kuchler
  • Article
    | Open Access

    The scaffold protein Scribble (Scrib) has roles in PCP and tight junction formation. Here the authors show that during embryo implantation in mouse, Scrib is needed to form the avascular primary decidual zone by transforming stromal cells into an epithelial cell-like barrier around the crypt, protecting the embryo from harmful infiltrations.

    • Jia Yuan
    • , Shizu Aikawa
    • , Wenbo Deng
    • , Amanda Bartos
    • , Gerd Walz
    • , Florian Grahammer
    • , Tobias B. Huber
    • , Xiaofei Sun
    •  & Sudhansu K. Dey
  • Article
    | Open Access

    Established bacterial glycoengineering platforms limit access to protein and glycan substrates. Here the authors design a cytoplasmic protein glycosylation system, Glycoli, to generate a variety of multivalent glycostructures.

    • Hanne L. P. Tytgat
    • , Chia-wei Lin
    • , Mikail D. Levasseur
    • , Markus B. Tomek
    • , Christoph Rutschmann
    • , Jacqueline Mock
    • , Nora Liebscher
    • , Naohiro Terasaka
    • , Yusuke Azuma
    • , Michael Wetter
    • , Martin F. Bachmann
    • , Donald Hilvert
    • , Markus Aebi
    •  & Timothy G. Keys
  • Article
    | Open Access

    Constructing biosynthetic pathways to study and engineer glycoprotein structures is difficult. Here, the authors use GlycoPRIME, a cell-free workflow for mixing-and-matching glycosylation enzymes, to evaluate 37 putative glycosylation pathways and discover routes to 18 new glycoprotein structures

    • Weston Kightlinger
    • , Katherine E. Duncker
    • , Ashvita Ramesh
    • , Ariel H. Thames
    • , Aravind Natarajan
    • , Jessica C. Stark
    • , Allen Yang
    • , Liang Lin
    • , Milan Mrksich
    • , Matthew P. DeLisa
    •  & Michael C. Jewett
  • Article
    | Open Access

    The invasion of epithelial tumours often depends on the epithelial-mesenchymal transition. Here, the authors report that intracellular activation of thyroid hormone by the D2 deiodinase enzyme promotes invasion and progression of squamous cell carcinoma by transcriptionally up-regulating ZEB-1.

    • Caterina Miro
    • , Emery Di Cicco
    • , Raffaele Ambrosio
    • , Giuseppina Mancino
    • , Daniela Di Girolamo
    • , Annunziata Gaetana Cicatiello
    • , Serena Sagliocchi
    • , Annarita Nappi
    • , Maria Angela De Stefano
    • , Cristina Luongo
    • , Dario Antonini
    • , Feliciano Visconte
    • , Silvia Varricchio
    • , Gennaro Ilardi
    • , Luigi Del Vecchio
    • , Stefania Staibano
    • , Anita Boelen
    • , Cedric Blanpain
    • , Caterina Missero
    • , Domenico Salvatore
    •  & Monica Dentice
  • Article
    | Open Access

    The coordination of interactions between multiple regulatory elements and genes within a chromatin domain remains poorly understood. Here, the authors use a method to detect multi-way chromatin interactions in a mouse model in which the α-globin domain is extended to include several additional genes, finding that the promoters do not form mutually exclusive interactions with the enhancers, but all interact simultaneously in a single complex.

    • A. Marieke Oudelaar
    • , Caroline L. Harrold
    • , Lars L. P. Hanssen
    • , Jelena M. Telenius
    • , Douglas R. Higgs
    •  & Jim R. Hughes
  • Article
    | Open Access

    ISG15 is a ubiquitin-like modifier that can be upregulated in response to bacterial infections. Here, the authors use proteomics to identify endogenous ISGylation substrates in the liver of Listeria monocytogenes infected mice and show that ISGylation alters basal and infection-induced autophagy.

    • Yifeng Zhang
    • , Fabien Thery
    • , Nicholas C. Wu
    • , Emma K. Luhmann
    • , Olivier Dussurget
    • , Mariko Foecke
    • , Clara Bredow
    • , Daniel Jiménez-Fernández
    • , Kevin Leandro
    • , Antje Beling
    • , Klaus-Peter Knobeloch
    • , Francis Impens
    • , Pascale Cossart
    •  & Lilliana Radoshevich
  • Article
    | Open Access

    It is unclear whether fallopian tube epithelium or ovarian surface epithelium is the cell-of-origin of high grade serous ovarian carcinoma (HGSOC). Here the authors report a dualistic origin for HGSOC using genetically engineered mouse models and observe differential chemotherapy sensitivity depending on the cell-of-origin.

    • Shuang Zhang
    • , Igor Dolgalev
    • , Tao Zhang
    • , Hao Ran
    • , Douglas A. Levine
    •  & Benjamin G. Neel
  • Article
    | Open Access

    In Drosophila, dosage compensation involves a twofold transcriptional upregulation of the single male chromosome X. Here the authors show that global conformational differences are specifically present in the male X chromosome and detectable using Hi-C data, indicating that dosage compensation affects global chromosome structure.

    • Koustav Pal
    • , Mattia Forcato
    • , Daniel Jost
    • , Thomas Sexton
    • , Cédric Vaillant
    • , Elisa Salviato
    • , Emilia Maria Cristina Mazza
    • , Enrico Lugli
    • , Giacomo Cavalli
    •  & Francesco Ferrari
  • Article
    | Open Access

    The chromosomal kinase JIL-1 is responsible for interphase histone H3S10 phosphorylation and has been proposed to protect active chromatin from heterochromatinisation. Here, the authors show that JIL-1 is stabilized and anchored to active genes and telomeric transposons by JASPer, which binds to H3K36me3 nucleosomes via its PWWP domain.

    • Christian Albig
    • , Chao Wang
    • , Geoffrey P. Dann
    • , Felix Wojcik
    • , Tamás Schauer
    • , Silke Krause
    • , Sylvain Maenner
    • , Weili Cai
    • , Yeran Li
    • , Jack Girton
    • , Tom W. Muir
    • , Jørgen Johansen
    • , Kristen M. Johansen
    • , Peter B. Becker
    •  & Catherine Regnard
  • Article
    | Open Access

    Skewing of X chromosome inactivation (XCI) occurs when the silencing of one parental X chromosome is non-random. Here, Zito et al. report XCI patterns in lymphoblastoid cell lines, blood, subcutaneous adipose tissue samples and skin samples of monozygotic and dizygotic twins and find XCI skew to associate with tissue and age.

    • Antonino Zito
    • , Matthew N. Davies
    • , Pei-Chien Tsai
    • , Susanna Roberts
    • , Rosa Andres-Ejarque
    • , Stefano Nardone
    • , Jordana T. Bell
    • , Chloe C. Y. Wong
    •  & Kerrin S. Small
  • Article
    | Open Access

    The endoplasmic reticulum (ER) is an intracellular network characterized by highly dynamic behavior whose control mechanisms are unclear. Here, the authors show that the ER-membrane protein Reticulon (Rtnl1) can constrict ER bilayers and lead to ER fission.

    • Javier Espadas
    • , Diana Pendin
    • , Rebeca Bocanegra
    • , Artur Escalada
    • , Giulia Misticoni
    • , Tatiana Trevisan
    • , Ariana Velasco del Olmo
    • , Aldo Montagna
    • , Sergio Bova
    • , Borja Ibarra
    • , Peter I. Kuzmin
    • , Pavel V. Bashkirov
    • , Anna V. Shnyrova
    • , Vadim A. Frolov
    •  & Andrea Daga
  • Article
    | Open Access

    The ATR pathway is active during DNA replication stress to maintain genome stability. Here the authors reveal the role of the zinc finger containing protein 161 (ZFP161) to facilitate replication fork stability by acting as a scaffold to facilitate the interaction between RPA and ATR/ATRIP.

    • Wootae Kim
    • , Fei Zhao
    • , Rentian Wu
    • , Sisi Qin
    • , Somaira Nowsheen
    • , Jinzhou Huang
    • , Qin Zhou
    • , Yuping Chen
    • , Min Deng
    • , Guijie Guo
    • , Kuntian Luo
    • , Zhenkun Lou
    •  & Jian Yuan
  • Article
    | Open Access

    Cellular actin networks can be rapidly disassembled and remodeled in a few seconds, yet in vitro actin filaments depolymerize over minutes. Here the authors show that Cyclase-associated protein (CAP) and Cofilin synergize to processively depolymerize actin filament pointed ends 330-fold faster than spontaneous depolymerization.

    • Shashank Shekhar
    • , Johnson Chung
    • , Jane Kondev
    • , Jeff Gelles
    •  & Bruce L. Goode
  • Article
    | Open Access

    The extracellular cues regulating filamentous actin formation in somatic cell nuclei are unclear. Here, the authors show that activated GPCR signalling initiates transient accumulation of nuclear F-actin/formation in nuclear actin filaments, driven by calcium and requiring the nucleator Formin INF2.

    • Ying Wang
    • , Alice Sherrard
    • , Bing Zhao
    • , Michael Melak
    • , Jonathan Trautwein
    • , Eva-Maria Kleinschnitz
    • , Nikolaos Tsopoulidis
    • , Oliver T. Fackler
    • , Carsten Schwan
    •  & Robert Grosse
  • Article
    | Open Access

    The molecular mechanisms of mitochondrial dysfunction in the premature ageing Werner syndrome were elusive. Here the authors show that NAD+ depletion-induced impaired mitophagy contributes to this phenomenon, shedding light on potential therapeutics.

    • Evandro F. Fang
    • , Yujun Hou
    • , Sofie Lautrup
    • , Martin Borch Jensen
    • , Beimeng Yang
    • , Tanima SenGupta
    • , Domenica Caponio
    • , Rojyar Khezri
    • , Tyler G. Demarest
    • , Yahyah Aman
    • , David Figueroa
    • , Marya Morevati
    • , Ho-Joon Lee
    • , Hisaya Kato
    • , Henok Kassahun
    • , Jong-Hyuk Lee
    • , Deborah Filippelli
    • , Mustafa Nazir Okur
    • , Aswin Mangerich
    • , Deborah L. Croteau
    • , Yoshiro Maezawa
    • , Costas A. Lyssiotis
    • , Jun Tao
    • , Koutaro Yokote
    • , Tor Erik Rusten
    • , Mark P. Mattson
    • , Heinrich Jasper
    • , Hilde Nilsen
    •  & Vilhelm A. Bohr
  • Article
    | Open Access

    Mitochondrial calcium signaling plays an important role in neuronal bioenergetics yet its regulation by brain activity in vivo is not understood. Here, the authors show that mitochondrial and cytosolic calcium transients are dynamically coupled as a function of brain activity.

    • Yuan Lin
    • , Lin-Lin Li
    • , Wei Nie
    • , Xiaolei Liu
    • , Avital Adler
    • , Chi Xiao
    • , Fujian Lu
    • , Liping Wang
    • , Hua Han
    • , Xianhua Wang
    • , Wen-Biao Gan
    •  & Heping Cheng