Post-translational modifications articles within Nature Communications

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• Article
  22 April 2024 | Open Access

  Tyrosine phosphorylation of CARM1 promotes its enzymatic activity and alters its target specificity

  Coactivator-associated arginine methyltransferase 1 (CARM1) is an important target in hematologic malignancies. In this work, the authors show that the hyperactivation of Janus kinase 2 (JAK2) by the V617F mutation phosphorylates CARM1 which regulates its methyltransferase activity and alters its target specificity.

  • Hidehiro Itonaga
  • , Adnan K. Mookhtiar
  •  & Stephen D. Nimer

• Article
  15 April 2024 | Open Access

  Reciprocal antagonism of PIN1-APC/C^CDH1 governs mitotic protein stability and cell cycle entry

  Unveiling the regulation of mitotic protein degradation is crucial for cancer therapy. Here, the authors reveal that a reciprocal inhibition of PIN1-APC/C^CDH1 controls the cell cycle and mitotic protein degradation, offering a synergistic anti-tumor strategy.

  • Shizhong Ke
  • , Fabin Dang
  •  & Kun Ping Lu

• Article
  13 April 2024 | Open Access

  Dynamics of DNA damage-induced nuclear inclusions are regulated by SUMOylation of Btn2

  Maintaining a healthy nuclear proteome during DNA damage is important but its regulation is poorly understood. The authors here show that a SUMO modification of the small heat shock protein Btn2 regulates yeast nuclear protein sequestration during stress.

  • Arun Kumar
  • , Veena Mathew
  •  & Peter C. Stirling

• Article
  11 April 2024 | Open Access

  Nardilysin-regulated scission mechanism activates polo-like kinase 3 to suppress the development of pancreatic cancer

  Polo-like kinase 3 (Plk3) has a tumor suppressive role through the induction of apoptosis, however, the mechanism underlying its activation is unclear. Here, in pancreatic cancer, the authors show that activation of Plk3 is dependent on its cleavage into p41Plk3, by the metalloendopeptidase nardilysin.

  • Jie Fu
  • , Jianhua Ling
  •  & Paul J. Chiao

• Article
  11 April 2024 | Open Access

  Pathogenic mutations of human phosphorylation sites affect protein–protein interactions

  Here the authors characterise the impact of phosphorylation site mutations in intrinsically disordered regions (IDRs) on protein-protein interactions, highlighting the critical role of phosphorylation of IDRs in health and disease.

  • Trendelina Rrustemi
  • , Katrina Meyer
  •  & Matthias Selbach

• Article
  06 April 2024 | Open Access

  Systematic HOIP interactome profiling reveals critical roles of linear ubiquitination in tissue homeostasis

  Authors perform an in vivo mass spectrometry-based interactome analysis of HOIL-1-interacting protein, a key component of linear ubiquitination assembly complex.

  • Yesheng Fu
  • , Lei Li
  •  & Lingqiang Zhang

• Article
  03 April 2024 | Open Access

  Dbf4-dependent kinase promotes cell cycle controlled resection of DNA double-strand breaks and repair by homologous recombination

  The repair of DNA double strand breaks is strictly controlled during the cell cycle by the CDK kinase. Here the authors identify the DDK kinase as a second major regulator for this cell cycle regulation and elucidate its functional targets.

  • Lorenzo Galanti
  • , Martina Peritore
  •  & Boris Pfander

• Article
  02 April 2024 | Open Access

  Involution of brown adipose tissue through a Syntaxin 4 dependent pyroptosis pathway

  Aging, chronic high-fat diet feeding, or housing at thermoneutrality induces brown adipose tissue (BAT) involution. Here, the authors demonstrate that physiologic aging induced involution and thermogenic dysfunction result from pyroptotic signalling activation.

  • Xiaofan Yu
  • , Gabrielle Benitez
  •  & Daorong Feng

• Article
  01 April 2024 | Open Access

  Loss-of-function mutation in PRMT9 causes abnormal synapse development by dysregulation of RNA alternative splicing

  Mutations in protein arginine methyltransferase 9 (PRMT9) are linked to intellectual disability. Here, the authors show that mutant PRMT9 fails to methylate its primary substrate SF3B2, causing aberrant RNA splicing and abnormal synapse development.

  • Lei Shen
  • , Xiaokuang Ma
  •  & Yanzhong Yang

• Article
  28 March 2024 | Open Access

  Casein kinase II promotes piRNA production through direct phosphorylation of USTC component TOFU-4

  How the production of piRNA is regulated remains elusive. Here the authors showed that casein kinase II mediated direct phosphorylation of USTC component TOFU-4 promotes piRNA production.

  • Gangming Zhang
  • , Chunwei Zheng
  •  & Craig Mello

• Article
  23 March 2024 | Open Access

  Ion mobility-tandem mass spectrometry of mucin-type O-glycans

  Currently, only a few specialized labs can characterize O-glycans. The present study couples high-resolution ion mobility spectrometry with tandem mass spectrometry to efficiently identify complex O-glycan structures in clinical samples.

  • Leïla Bechtella
  • , Jin Chunsheng
  •  & Kevin Pagel

• Article
  22 March 2024 | Open Access

  The aldehyde dehydrogenase 2 rs671 variant enhances amyloid β pathology

  Here, Wang et al. report that the ALDH2 rs671 variant exacerbates amyloid-β pathology in the human brain. Mechanistically, the variant leads to 4-HNE accumulation, adducting Lys53 of C99 and promoting the production of Aβ40.

  • Xia Wang
  • , Jiayu Wang
  •  & Wei Ge

• Article
  20 March 2024 | Open Access

  A structure-based designed small molecule depletes hRpn13^Pru and a select group of KEN box proteins

  Here, the authors identify a small molecule degrader (XL44) for hRpn13 and solve the XL44-hRpn13 structure. XL44 induces apoptosis in myeloma cells with hRpn13 dependency and also targets KEN box proteins PCLAF and RRM2. Loss of hRpn13 and PCLAF abrogates XL44 restriction of cell viability.

  • Xiuxiu Lu
  • , Monika Chandravanshi
  •  & Kylie J. Walters

• Article
  19 March 2024 | Open Access

  VCF1 is a p97/VCP cofactor promoting recognition of ubiquitylated p97-UFD1-NPL4 substrates

  p97/VCP, a nexus of the ubiquitin system, recognizes and unfolds ubiquitylated substrates via multiple cofactors. Here, the authors identify VCF1, a nuclear cofactor promoting p97 recruitment to, and proteasomal degradation of, ubiquitylated targets.

  • Ann Schirin Mirsanaye
  • , Saskia Hoffmann
  •  & Niels Mailand

• Article
  18 March 2024 | Open Access

  Cryo-EM structures of type IV pili complexed with nanobodies reveal immune escape mechanisms

  Bacterial type IV pili are filamentous cell surface structures and candidate targets for vaccine development. Here, authors determine how antibodies interact with pili at the structural level providing insight into immune escape mechanisms and potential countermeasures.

  • David Fernandez-Martinez
  • , Youxin Kong
  •  & Guillaume Duménil

• Article
  16 March 2024 | Open Access

  Therapeutic targeting nudix hydrolase 1 creates a MYC-driven metabolic vulnerability

  MYC oncogene promotes tumourigenesis by coordinating cancer cell proliferation with metabolic adaptation to the consequent excessive oxidative stress. Here, the authors show that nudix hydrolase 1 (NUDT1) is a MYC-driven metabolic vulnerability and generate a NUDT1 protein degrader to treat preclinical MYC-associated cancer.

  • Minhui Ye
  • , Yingzhe Fang
  •  & Guoliang Qing

• Article
  13 March 2024 | Open Access

  NME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia

  NME3 is a member of NDPK family. Here, Chen et. al., discover that histidine phosphorylatable NME3 is required for hypoxia-induced mitophagy via PA-dependent interaction with Drp1, which is protected from MUL1-mediated ubiquitination for mitophagy.

  • Chih-Wei Chen
  • , Chi Su
  •  & Zee-Fen Chang

• Article
  13 March 2024 | Open Access

  Biallelic NAA60 variants with impaired n-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications

  Most individuals with primary familial brain calcification (PFBC) remain genetically unsolved. Here the authors show that NAA60 biallelic variants cause PFBC, likely via reduced N-terminal acetylation and SLC20A2 levels with impaired phosphate uptake.

  • Viorica Chelban
  • , Henriette Aksnes
  •  & Henry Houlden

• Article
  06 March 2024 | Open Access

  Microtubule damage shapes the acetylation gradient

  Microtubules are acetylated on the inside of their hollow lumen, a modification linked to their lifespan. Here, the authors show that damage holes act as entry points for a deacetylase to access the lumen, thereby locally counteracting acetylation.

  • Mireia Andreu-Carbó
  • , Cornelia Egoldt
  •  & Charlotte Aumeier

• Article
  05 March 2024 | Open Access

  DJ-1 protects proteins from acylation by catalyzing the hydrolysis of highly reactive cyclic 3-phosphoglyceric anhydride

  Human protein DJ-1 displays neuroprotective properties. Here, the authors demonstrate that DJ-1 hydrolyzes cyclic 3-phosphoglyceric anhydride (cPGA), thereby protecting proteins from acylation by this highly reactive metabolite spontaneously forming in glycolysis.

  • Aizhan Akhmadi
  • , Adilkhan Yeskendir
  •  & Darkhan Utepbergenov

• Article
  17 February 2024 | Open Access

  Spatiotemporal and direct capturing global substrates of lysine-modifying enzymes in living cells

  Here the authors report a strategy to directly capture substrates of lysine-modifying enzymes via post-translational modification (PTM)-acceptor residue crosslinking in living cells, enabling global profiling of substrates of PTM-enzymes and validation of PTM-sites in a straightforward manner.

  • Hao Hu
  • , Wei Hu
  •  & Xiao-Hua Chen

• Article
  15 February 2024 | Open Access

  The Eyes Absent family members EYA4 and EYA1 promote PLK1 activation and successful mitosis through tyrosine dephosphorylation

  The Eyes Absent proteins (EYA1-4) are a group of tyrosine phosphatases. Here, the authors report a signalling pathway in which EYA4 and EYA1 dephosphorylate Polo-like kinase 1 (PLK1) at pY445 to support PLK1 activation and mitosis.

  • Christopher B. Nelson
  • , Samuel Rogers
  •  & Hilda A. Pickett

• Article
  10 February 2024 | Open Access

  Structure-guided engineering enables E3 ligase-free and versatile protein ubiquitination via UBE2E1

  Ubiquitin E3 ligases are key to accessing ubiquitinated proteins, but only a few substrates have defined E3 ligases. Here, the authors reveal the mechanism of naturally occurring E3-independent ubiquitination and develop an E3-free enzymatic strategy for the versatile generation of ubiquitinated proteins.

  • Xiangwei Wu
  • , Yunxiang Du
  •  & Lei Liu

• Article
  31 January 2024 | Open Access

  Ubiquitin ligase RNF20 coordinates sequential adipose thermogenesis with brown and beige fat-specific substrates

  Upon cold exposure, two types of thermogenic fat cells, brown and beige adipocytes, are sequentially activated. Here, the authors show that E3 ubiquitin ligase RNF20 coordinates the sequential thermogenic activation through fat depot specific substrates.

  • Yong Geun Jeon
  • , Hahn Nahmgoong
  •  & Jae Bum Kim

• Article
  19 January 2024 | Open Access

  The CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8⁺ T cells

  CD8 + T cells are central players in anti-tumour immunity. Here authors identify Cul5, a ubiquitin E3 ligase as an important inhibitor of CD8 + T cell anti-tumour cytotoxicity and persistence via involvement with both T cell receptor and cytokine-regulated central pathways.

  • Xiaofeng Liao
  • , Wenxue Li
  •  & Dianqing Wu

• Article
  15 January 2024 | Open Access

  The phosphatase DUSP22 inhibits UBR2-mediated K63-ubiquitination and activation of Lck downstream of TCR signalling

  The T cell receptor signalosome integrates multiple positive and negative regulatory elements to finetune the response and limit harmful inflammation. Here authors show a regulatory cascade of T cell activation, in which DUSP22 negatively regulates UBR2, which is an activator of the kinase Lck via K63 ubiquitination.

  • Ying-Chun Shih
  • , Hsueh-Fen Chen
  •  & Tse-Hua Tan

• Article
  09 January 2024 | Open Access

  N-linked Fc glycosylation is not required for IgG-B-cell receptor function in a GC-derived B-cell line

  IgG molecules are glycosylated at a conserved asparagine residue of their constant region, and this modification is essential for the effector functions of their soluble form, such as complement activation and binding to Fcɣ receptors. Here authors show that in a model B-cell line, neither the expression nor the function of the membrane-bound form of IgG depend on glycosylation.

  • Theresa Kissel
  • , Veerle F. A. M. Derksen
  •  & René E. M. Toes

• Article
  06 January 2024 | Open Access

  A role and mechanism for redox sensing by SENP1 in β-cell responses to high fat feeding

  Insulin secretion adapts to metabolic needs, but how this happens over the short term is not clear. Here the authors show this involves upregulation of beta-cell exocytosis and requires the SUMO-protease SENP1, which responds to redox state in a zinc-dependent manner.

  • Haopeng Lin
  • , Kunimasa Suzuki
  •  & Patrick E. MacDonald

• Article
  04 January 2024 | Open Access

  TRIM28-mediated nucleocapsid protein SUMOylation enhances SARS-CoV-2 virulence

  Here, the authors show that TRIM28-mediated SUMOylation of SARS-CoV-2 NP is critical for its liquid-liquid phase separation (LLPS) property and subsequent inhibition of innate antiviral immunity. The peptide NSIP-III is applied to unleash such connection by interfering TRIM28 and NP interaction.

  • Jiang Ren
  • , Shuai Wang
  •  & Long Zhang

• Article
  02 January 2024 | Open Access

  Covalent PARylation of DNA base excision repair proteins regulates DNA demethylation

  The PARylation activity of PARP recruits DNA repair proteins to damaged DNA, most likely via non-covalent protein-PAR interactions. Here, the authors show that PARP1 covalently PARylates base excision repair proteins to modulate their DNA transactions and thus promote active BER DNA demethylation.

  • Simon D. Schwarz
  • , Jianming Xu
  •  & Roland Steinacher

• Article
  02 January 2024 | Open Access

  Stabilization of Pin1 by USP34 promotes Ubc9 isomerization and protein sumoylation in glioma stem cells

  Post-translational modifications including protein sumoylation is under specific regulation in glioma stem cells (GSCs). Here, the authors show that Pin1 is deubiquitinated and stabilized by USP34, which in turn promotes isomerization of Ubc9, leading to SUMO1-modified global hypersumoylation to maintain the tumorigenic capacity of GSCs.

  • Qiuhong Zhu
  • , Panpan Liang
  •  & Wenchao Zhou

• Article
  21 December 2023 | Open Access

  The Mycobacterium tuberculosis methyltransferase Rv2067c manipulates host epigenetic programming to promote its own survival

  Singh et al. show how the M. tuberculosis methyltransferase Rv2067c outsmarts host epigenetic machinery by methylating histone H3 prior to its assembly into nucleosomes, thereby ensuring the pathogen’s intracellular survival/success.

  • Prakruti R. Singh
  • , Venkatareddy Dadireddy
  •  & Valakunja Nagaraja

• Article
  18 December 2023 | Open Access

  Autophagy of OTUD5 destabilizes GPX4 to confer ferroptosis-dependent kidney injury

  Understanding the role of GPX4 in cell ferroptosis at the interface of the inner cortex and medulla is crucial in the context of renal injury. Here, the authors demonstrate that the OTUD5 interaction with GPX4 is key in resisting ischemia/reperfusion-induced ferroptosis in renal cells, offering a new strategy for treating acute kidney injury.

  • Li-Kai Chu
  • , Xu Cao
  •  & Jun Liu

• Article
  18 December 2023 | Open Access

  Acetylation is required for full activation of the NLRP3 inflammasome

  The NLRP3 inflammasome is activated in two steps, priming and assembly, in response to endogenous, microbial, and other environmental danger signals. Here authors show that the assembly step is regulated by acetylation, and inhibition of this post-translational modification prevents full activation of the inflammasome.

  • Yening Zhang
  • , Ling Luo
  •  & Kai Zhao

• Article
  15 December 2023 | Open Access

  MYOD-SKP2 axis boosts tumorigenesis in fusion negative rhabdomyosarcoma by preventing differentiation through p57^Kip2 targeting

  SKP2 is an oncogenic E3-ubiquitin ligase. Here the authors show that SKP2 is epigenetically regulated by the muscle lineage transcription factor MYOD, supports tumorigenesis in the Fusion Negative (FN) subtype of rhabdomyosarcoma (RMS) and impairs differentiation promoting degradation of p57^Kip2.

  • Silvia Pomella
  • , Matteo Cassandri
  •  & Rossella Rota

• Article
  14 December 2023 | Open Access

  Ubiquitination-mediated Golgi-to-endosome sorting determines the toxin-antidote duality of fission yeast wtf meiotic drivers

  Meiotic drivers of the wtf family kill progeny lacking the driver by producing a toxin and an antidote. Here, authors reveal that ubiquitination-mediated sorting of the antidote prevents it from becoming toxic and enables it to neutralize the toxin.

  • Jin-Xin Zheng
  • , Tong-Yang Du
  •  & Li-Lin Du

• Article
  14 December 2023 | Open Access

  Profiling ubiquitin signalling with UBIMAX reveals DNA damage- and SCF^β-Trcp1-dependent ubiquitylation of the actin-organizing protein Dbn1

  Using Xenopus egg extracts, the authors developed a mass spectrometry method (UBIMAX) to identify proteins ubiquitylated in response to defined DNA lesions. Highlighting UBIMAX’s versatility, they describe the ubiquitylation of the actin regulator Dbn1 in response to DNA double-strand breaks.

  • Camilla S. Colding-Christensen
  • , Ellen S. Kakulidis
  •  & Michael L. Nielsen

• Article
  14 December 2023 | Open Access

  Remodeling of the ribosomal quality control and integrated stress response by viral ubiquitin deconjugases

  Here, the authors show how the vDUB from the large tegument protein from the human herpes virus can reprogram translation in host cells by modulating the activity of the ribosome quality machinery and activating the integrated stress response.

  • Jiangnan Liu
  • , Noemi Nagy
  •  & Maria G. Masucci

• Article
  12 December 2023 | Open Access

  Nuclear cGAS restricts L1 retrotransposition by promoting TRIM41-mediated ORF2p ubiquitination and degradation

  Zhen and colleagues show that nuclear cGAS represses L1 retrotransposition to stabilize the genome by enhancing the interaction between ORF2p and the E3 ligase TRIM41 upon DNA damage, which leads to the ubiquitination and degradation of ORF2p.

  • Zhengyi Zhen
  • , Yu Chen
  •  & Zhiyong Mao

• Article
  12 December 2023 | Open Access

  The assembly of the Mitochondrial Complex I Assembly complex uncovers a redox pathway coordination

  The role that cellular bioenergetics plays in the early stages of Alzheimer’s disease is poorly understood. Here the authors describe structures of key OXPHOS assembly proteins, providing insights into how these pathways are interlinked and regulated.

  • Lindsay McGregor
  • , Samira Acajjaoui
  •  & Montserrat Soler-Lopez

• Article
  08 December 2023 | Open Access

  Structure of the complete Saccharomyces cerevisiae Rpd3S-nucleosome complex

  In this study, the authors present the cryogenic electron microscopy reconstruction of the Rpd3S complex engaged with a nucleosome. The corresponding model describes the interactions that facilitate histone deacetylation within gene bodies by the Rpd3S complex.

  • Jonathan W. Markert
  • , Seychelle M. Vos
  •  & Lucas Farnung

• Article
  08 December 2023 | Open Access

  Characterization of nucleolar SUMO isopeptidases unveils a general p53-independent checkpoint of impaired ribosome biogenesis

  Ribosome biogenesis is tightly coordinated with cell-cycle progression. By characterizing the SUMO isopeptidases SENP3/SENP5, Doenig et al. identify a long-sought p53-independent impaired ribosome checkpoint that converges on downregulation of CDK6.

  • Judith Dönig
  • , Hannah Mende
  •  & Stefan Müller

• Article
  06 December 2023 | Open Access

  Acetylation regulates the oligomerization state and activity of RNase J, the Helicobacter pylori major ribonuclease

  Here the authors find that RNase J, the major ribonuclease of the gastric pathogen Helicobacter pylori is post-translationally modified by acetylation. They show that acetylation can control RNase J activity.

  • Alejandro Tejada-Arranz
  • , Aleksei Lulla
  •  & Hilde De Reuse

• Article
  30 November 2023 | Open Access

  CaMKK2 and CHK1 phosphorylate human STN1 in response to replication stress to protect stalled forks from aberrant resection

  Here the authors show that the calcium-sensing kinase CaMKK2 phosphorylates STN1 in response to replication stress and elevated cytosolic calcium concentration to protect stalled replication forks from aberrant MRE11 degradation. Cancer-associated STN1 mutations abolish STN1 phosphorylation, resulting in fork instability.

  • Rishi Kumar Jaiswal
  • , Kai-Hang Lei
  •  & Weihang Chai

• Article
  23 November 2023 | Open Access

  BioE3 identifies specific substrates of ubiquitin E3 ligases

  Here, the authors describe BioE3, a biotin-based method to discriminate direct substrates of ubiquitin E3 ligases of interest from mere interactors using proximity proteomics. BioE3 responds to chemical treatments, and works with RING- and HECT-type E3s, as well as ubiquitin-likes (e.g., SUMO).

  • Orhi Barroso-Gomila
  • , Laura Merino-Cacho
  •  & James D. Sutherland

• Article
  21 November 2023 | Open Access

  PTK2B promotes TBK1 and STING oligomerization and enhances the STING-TBK1 signaling

  TBK1 plays a central role in the antiviral innate response. Here the authors identify PTK2B as an interacting protein linked to TBK1 and STING oligomerisation and the activation of STING-TBK1 signaling.

  • Yongfang Lin
  • , Jing Yang
  •  & Qinmiao Sun

• Article
  17 November 2023 | Open Access

  SEPTIN2 suppresses an IFN-γ-independent, proinflammatory macrophage activation pathway

  Interferon-gamma (IFN-γ) is an important but not exclusive proinflammatory mediator in macrophages. Here authors show that IFN-γ-independent macrophage autoactivation involves endoplasmic reticulum (ER) stress which in turn induces the GTP-binding protein Septin2 to limit inflammation via a negative feedback loop.

  • Beibei Fu
  • , Yan Xiong
  •  & Haibo Wu

• Article
  13 November 2023 | Open Access

  Functional and structural diversity in deubiquitinases of the Chlamydia-like bacterium Simkania negevensis

  Intracellular bacteria use deubiquitinase effectors to avoid being targeted for autophagic clearance. The authors show that the Chlamydia-like bacterium Simkania negevensis encodes an unusually broad range of these enzymes, including members that specifically target linear and K6-linked ubiquitin chains.

  • Vanessa Boll
  • , Thomas Hermanns
  •  & Kay Hofmann

• Article
  11 November 2023 | Open Access

  The E3 ligase Riplet promotes RIG-I signaling independent of RIG-I oligomerization

  Riplet conjugates K63-Ub chain to RIG-I in order to induce a robust antiviral response, but the mechanism of action remains unclear. Here, the authors show that Riplet recognizes RIG-I regardless of its RNA-bound status and promotes RIG-I signaling independent of RIG-I oligomerization.

  • Wenshuai Wang
  • , Benjamin Götte
  •  & Anna Marie Pyle

• Article
  11 November 2023 | Open Access

  SARS-CoV-2 hijacks a cell damage response, which induces transcription of a more efficient Spike S-acyltransferase

  The fusogenic activity of SARS-CoV-2 Spike depends on its post-translational lipid modification by host S-acyltransferases, predominantly ZDHHC20. Here, Mesquita and Abrami et al. show that SARS-CoV-2 infection and colitis in mice induce a damage response resulting in an altered version of the ZDHHC20 enzyme that is more abundant and significantly more efficient at attaching fatty acids to viral Spike.

  • Francisco S. Mesquita
  • , Laurence Abrami
  •  & F. Gisou van der Goot