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ROS-dependent S-palmitoylation activates cleaved and intact gasdermin D
- Gang Du
- , Liam B. Healy
- & Hao Wu
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Proteome-scale discovery of protein degradation and stabilization effectors
A synthetic proteome-scale strategy enables the identification of a diverse range of human proteins that can induce the degradation or stabilization of a target protein in a proximity-dependent way.
- Juline Poirson
- , Hanna Cho
- & Mikko Taipale
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UFM1 E3 ligase promotes recycling of 60S ribosomal subunits from the ER
Structural and biochemical analyses reveal details of how UFM1 conjugation and deconjugation mediate ribosome recycling and quality control.
- Paul A. DaRosa
- , Ivan Penchev
- & Ron R. Kopito
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| Open AccessThe UFM1 E3 ligase recognizes and releases 60S ribosomes from ER translocons
Attachment of the ubiquitin-like modifier UFM1 to 60S ribosomes has a critical function in the release and recycling of stalled or terminated ribosomes from the endoplasmic reticulum membrane.
- Linda Makhlouf
- , Joshua J. Peter
- & Yogesh Kulathu
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Disruption of sugar nucleotide clearance is a therapeutic vulnerability of cancer cells
An enzyme called UXS1 that converts one sugar nucleotide to another is needed more in some cancer cells than in normal cells, providing a potential weakness that can be exploited therapeutically.
- Mihir B. Doshi
- , Namgyu Lee
- & Dohoon Kim
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| Open AccessMacromolecular condensation buffers intracellular water potential
Water thermodynamics drive changes in macromolecular assembly that rapidly restore intracellular water availability in response to physiological fluctuations in temperature, pressure and osmotic strength.
- Joseph L. Watson
- , Estere Seinkmane
- & Emmanuel Derivery
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Acetyl-methyllysine marks chromatin at active transcription start sites
Cellular lysine residues can be both methylated and acetylated on the same sidechain to form Nε-acetyl-Nε-methyllysine (Kacme), which is found on histone H4 across a range of species and across mammalian tissues and is associated with active chromatin.
- William J. Lu-Culligan
- , Leah J. Connor
- & Matthew D. Simon
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Article
| Open AccessA viral ADP-ribosyltransferase attaches RNA chains to host proteins
Bacteriophage T4 uses an enzyme known as ADP-ribosyltransferase ModB to modify the translational apparatus of bacteria it infects, not only by ADP-ribosylating proteins, but also by attaching entire RNA chains in a process known as RNAylation.
- Maik Wolfram-Schauerte
- , Nadiia Pozhydaieva
- & Katharina Höfer
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| Open AccessTDP-43 forms amyloid filaments with a distinct fold in type A FTLD-TDP
Cryo-electron microscopy structures and mass spectrometry analyses show that TAR DNA-binding protein 43 (TDP-43) forms amyloid filaments with a distinct fold in type A frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) compared with TDP-43 filaments in type B FTLD-TDP and amyotrophic lateral sclerosis.
- Diana Arseni
- , Renren Chen
- & Benjamin Ryskeldi-Falcon
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| Open AccessDiverse modes of H3K36me3-guided nucleosomal deacetylation by Rpd3S
Structural and biochemical studies of the Saccharomyces cerevisiae Rpd3 small complex in free and H3K36me3 nucleosome-bound states reveal multiple nucleosome-binding modes and provide insights into mechanisms underlying epigenetic regulation by histone modification.
- Haipeng Guan
- , Pei Wang
- & Haitao Li
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| Open AccessUbiquitination regulates ER-phagy and remodelling of endoplasmic reticulum
Ubiquitination of the receptor FAM134B regulates ER-phagy and remodelling of the endoplasmic reticulum in response to cellular demands.
- Alexis González
- , Adriana Covarrubias-Pinto
- & Ivan Dikić
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| Open AccessHeteromeric clusters of ubiquitinated ER-shaping proteins drive ER-phagy
The membrane-shaping protein ARL6IP1 is involved in the selective degradation of the endoplasmic reticulum, and this process depends on its ubiquitination and interaction with other membrane-shaping proteins such as FAM134B.
- Hector Foronda
- , Yangxue Fu
- & Christian A. Hübner
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| Open AccessAn atlas of substrate specificities for the human serine/threonine kinome
Analysis of the kinase activity of 300 protein Ser/Thr kinases reveals that the substrate specificity of the kinome is substantially more diverse than expected and is driven extensively by negative selectivity
- Jared L. Johnson
- , Tomer M. Yaron
- & Lewis C. Cantley
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| Open AccessStructural basis of tankyrase activation by polymerization
Structural insights into the poly-ADP-ribosyltransferase tankyrase reveal its filamentous architecture and illustrate how assembly controls catalytic and non-catalytic functions.
- Nisha Pillay
- , Laura Mariotti
- & Sebastian Guettler
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The E3 ligase adapter cereblon targets the C-terminal cyclic imide degron
C-terminal cyclic imides are physiological degrons that enable the ubiquitin E3 ligase adapter protein cereblon to target substrates for degradation.
- Saki Ichikawa
- , Hope A. Flaxman
- & Christina M. Woo
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| Open AccessPost-translational control of beige fat biogenesis by PRDM16 stabilization
The ubiquitin E3 ligase CUL2–APPBP2 determines PRDM16 protein stability by catalysing PRDM16 polyubiquitination in beige fat.
- Qiang Wang
- , Huixia Li
- & Shingo Kajimura
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| Open AccessA peroxisomal ubiquitin ligase complex forms a retrotranslocation channel
The cryo-electron microscopy structure of the membrane-embedded ubiquitin ligase complex reveals its function as a retrotranslocation channel for shuttling mobile receptors out of peroxisomes.
- Peiqiang Feng
- , Xudong Wu
- & Tom A. Rapoport
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| Open AccessCore control principles of the eukaryotic cell cycle
The core cell cycle is largely driven by increasing total CDK activity together with minor differences in the substrate specificity of the CDKs initiating DNA replication and mitosis.
- Souradeep Basu
- , Jessica Greenwood
- & Paul Nurse
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Intracellular lipid surveillance by small G protein geranylgeranylation
In Caenorhabditis elegans, geranylgeranyl conjugation to RAB-11.1 acts as a lipid sensor to regulate nutrient uptake and lipid metabolism in response to metabolic demand.
- Abigail Watterson
- , Lexus Tatge
- & Peter M. Douglas
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Structural insights into Ubr1-mediated N-degron polyubiquitination
Structures of Ubr1 in complex with Ubc2, ubiquitin and two N-degron peptides reveal a Ubc2-binding region and an acceptor ubiquitin-binding loop on Ubr1, providing mechanistic insights into the initiation and elongation steps of ubiquitination catalysed by Ubr1.
- Man Pan
- , Qingyun Zheng
- & Minglei Zhao
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Shigella evades pyroptosis by arginine ADP-riboxanation of caspase-11
This study reports the identification of a new post-translational modification, termed ADP riboxanation, which is mediated by the Shigella effector OspC3 and inactivates the cytosolic LPS sensing pathway of caspase-4 and caspase-11.
- Zilin Li
- , Wang Liu
- & Feng Shao
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Mechanisms of BRCA1–BARD1 nucleosome recognition and ubiquitylation
The authors elucidate the mechanisms for the ubiquitylation specificity and recruitment of the ubiquitin ligase complex BRCA1–BARD1 to damaged DNA within chromatin to facilitate homologous recombination.
- Qi Hu
- , Maria Victoria Botuyan
- & Georges Mer
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MARK4 controls ischaemic heart failure through microtubule detyrosination
MARK4 regulates cardiomyocyte contractility by promoting MAP4 phosphorylation, which facilitates the access of VASH2 to microtubules for the detyrosination of α-tubulin; MARK4 deficiency after acute myocardial infarction limits the reduction in the left ventricular ejection fraction.
- Xian Yu
- , Xiao Chen
- & Xuan Li
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Ubiquitylation of lipopolysaccharide by RNF213 during bacterial infection
Upon Salmonella invasion of the mammalian cytosol, ubiquitylation of a non-proteinaceous substrate—the lipid A moiety of bacterial lipopolysaccharide—by the E3 ubiquitin ligase RNF213 marks the bacteria as cargo for antibacterial autophagy.
- Elsje G. Otten
- , Emma Werner
- & Felix Randow
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Elevated NSD3 histone methylation activity drives squamous cell lung cancer
The histone H3K36 methyltransferase NSD3, which is associated with the common 8p11–12 chromosomal amplification, is an oncogenic driver in lung squamous cell carcinoma.
- Gang Yuan
- , Natasha M. Flores
- & Or Gozani
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H1 histones control the epigenetic landscape by local chromatin compaction
Experiments using a conditional triple-knockout mouse strain show that histone H1 regulates the activity of chromatin domains by controlling chromatin compaction, genome architecture and histone methylation.
- Michael A. Willcockson
- , Sean E. Healton
- & Arthur I. Skoultchi
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Splicing factor YBX1 mediates persistence of JAK2-mutated neoplasms
Inhibition of YBX1, a downstream target of the Janus kinase JAK2, sensitizes myeloproliferative neoplasm cells to JAK and could provide a means to eradicate such cells in human haematopoietic cancers.
- Ashok Kumar Jayavelu
- , Tina M. Schnöder
- & Florian H. Heidel
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A STAT3 palmitoylation cycle promotes TH17 differentiation and colitis
The dynamic and reversible S-palmitoylation of the transcription factor STAT3 enhances its activation and promotes the differentiation of TH17 cells.
- Mingming Zhang
- , Lixing Zhou
- & Hening Lin
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Structural basis for dimerization quality control
Structural studies of the dimerization quality control E3 ubiquitin ligase SCF–FBXL17 indicate that its selectivity for aberrant complex formation is based on recognizing both shape and complementarity of interacting domains.
- Elijah L. Mena
- , Predrag Jevtić
- & Michael Rape
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Envelope protein ubiquitination drives entry and pathogenesis of Zika virus
The E3 ubiquitin ligase TRIM7 polyubiquitinates the envelope protein of Zika virus, adding Lys63-linked polyubiquitin chains that interact with the TIM1 receptor of host cells to enhance virus entry and replication.
- Maria I. Giraldo
- , Hongjie Xia
- & Ricardo Rajsbaum
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poly(UG)-tailed RNAs in genome protection and epigenetic inheritance
In Caenorhabditis elegans, the ribonucleotidyltransferase RDE-3 adds alternating uridine and guanosine ribonucleotides to the 3′ termini of RNAs, a key step in RNA interference and thus epigenetic inheritance in the C. elegans germline.
- Aditi Shukla
- , Jenny Yan
- & Scott Kennedy
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Ligand-induced monoubiquitination of BIK1 regulates plant immunity
The detection of microorganism-associated ligands by plant cells activates a signalling cascade in which the kinase BIK1 is monoubiquinated, released from the FLS2–BAK1 complex, and internalized by endocytosis.
- Xiyu Ma
- , Lucas A. N. Claus
- & Libo Shan
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Gene expression and cell identity controlled by anaphase-promoting complex
WDR5 and TBP recruit anaphase-promoting complex to specific transcription start sites in mitosis, initiating a ubiquitin-dependent mechanism that preserves cell identity by linking gene expression and cell division.
- Eugene Oh
- , Kevin G. Mark
- & Michael Rape
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HPF1 completes the PARP active site for DNA damage-induced ADP-ribosylation
Assembly of a catalytic centre formed by HPF1 bound to PARP1 or PARP2 is essential for protein ADP-ribosylation after DNA damage in human cells.
- Marcin J. Suskiewicz
- , Florian Zobel
- & Ivan Ahel
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Phase separation organizes the site of autophagosome formation
The pre-autophagosomal structure in yeast is a liquid-like condensate of Atg proteins whose phase separation may have a critical, active role in autophagy.
- Yuko Fujioka
- , Jahangir Md. Alam
- & Nobuo N. Noda
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Host-mediated ubiquitination of a mycobacterial protein suppresses immunity
Mycobacterium tuberculosis suppresses the production of inflammatory cytokines by host cells through the host-mediated ubiquitination of a mycobacterial protein, enhancing the interaction of a host signalling inhibitor with another signalling molecule.
- Lin Wang
- , Juehui Wu
- & Baoxue Ge
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Regulation of α-synuclein by chaperones in mammalian cells
Chaperones interact with a canonical motif in α-synuclein, which can be prevented by phosphorylation of α-synuclein at Tyr39, whereas inhibition of this interaction leads to the localization of α-synuclein to the mitochondria and aggregate formation.
- Björn M. Burmann
- , Juan A. Gerez
- & Sebastian Hiller
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Dynamic lineage priming is driven via direct enhancer regulation by ERK
ERK reversibly regulates embryonic stem cell transcription via selective redistribution of co-factors and RNA polymerase from pluripotency to early differentiation enhancers, while leaving transcription factors bound to their enhancers, thus preserving plasticity.
- William B. Hamilton
- , Yaron Mosesson
- & Joshua M. Brickman
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Structure of the Fanconi anaemia monoubiquitin ligase complex
The structure of the multiprotein Fanconi anaemia core complex, determined using cryo-electron microscopy and mass spectrometry, shows that the complex adopts an extended asymmetric structure and highlights the structural and functional asymmetry of the RING finger domains.
- Shabih Shakeel
- , Eeson Rajendra
- & Lori A. Passmore
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Metabolic regulation of gene expression by histone lactylation
The lactylation of lysine residues on histones in mammalian cells is stimulated by hypoxia and bacterial challenges, and increased histone lactylation induces genes involved in wound healing.
- Di Zhang
- , Zhanyun Tang
- & Yingming Zhao
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Insights into ubiquitin chain architecture using Ub-clipping
Enzymatic cleavage within ubiquitin molecules followed by quantitative mass-spectrometry simplifies complex ubiquitin chains and enables mapping of polyubiquitin architectures.
- Kirby N. Swatek
- , Joanne L. Usher
- & David Komander
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p38γ is essential for cell cycle progression and liver tumorigenesis
The stress-activated kinase p38γ has a role in regulating entry into the cell cycle; in the liver, it can induce cellular proliferation during regeneration and promote the development of hepatocellular carcinoma.
- Antonia Tomás-Loba
- , Elisa Manieri
- & Guadalupe Sabio
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Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3
In serotonin-rich tissues, tissue transglutaminase 2 is able to attach serotonin to a glutamine residue in histone H3; this modification mediates permissive gene expression in these tissues.
- Lorna A. Farrelly
- , Robert E. Thompson
- & Ian Maze
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PKG1-modified TSC2 regulates mTORC1 activity to counter adverse cardiac stress
Phosphorylation of one of two adjacent serine residues in TSC2 is both required and sufficient for PKG1-mediated cardiac protection against pressure overload in mice; these serine residues provide a genetic tool for the bidirectional regulation of stress-stimulated mTORC1 activity.
- Mark J. Ranek
- , Kristen M. Kokkonen-Simon
- & David A. Kass
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SETD3 is an actin histidine methyltransferase that prevents primary dystocia
SETD3 methylates mammalian actin at His73, and SETD3 deficiency impairs stimulus-induced contraction in primary human uterine smooth muscle cells and leads to maternal dystocia in mice.
- Alex W. Wilkinson
- , Jonathan Diep
- & Or Gozani
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Metabolic reprogramming by the S-nitroso-CoA reductase system protects against kidney injury
AKR1A1-regulated protein S-nitrosylation protects against kidney injury through PKM2-mediated metabolic reprogramming.
- Hua-Lin Zhou
- , Rongli Zhang
- & Jonathan S. Stamler
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Palladium-mediated enzyme activation suggests multiphase initiation of glycogenesis
The mechanism of glycogenesis, initiated by glycogenin, involves three distinct kinetic phases, with the final phase involving a refining process where only glucose is tolerated as a substrate.
- Matthew K. Bilyard
- , Henry J. Bailey
- & Benjamin G. Davis
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Kinase-controlled phase transition of membraneless organelles in mitosis
The dual-specificity kinase DYRK3 acts as a central ‘dissolvase’, mediating the phase transitions of several types of membraneless organelles during mitosis.
- Arpan Kumar Rai
- , Jia-Xuan Chen
- & Lucas Pelkmans
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OTULIN limits cell death and inflammation by deubiquitinating LUBAC
OTULIN, which removes ubiquitin chains deposited by LUBAC, promotes LUBAC activity by preventing its auto-ubiquitination, thereby supporting normal mouse embryo development and preventing pro-inflammatory cell death in adult mice.
- Klaus Heger
- , Katherine E. Wickliffe
- & Vishva M. Dixit