Andrii Gorelik
@andriigorelik.bsky.social
Sir Henry Wellcome Fellow | Oxford with Ivan Ahel & Harvard with Steve Gygi Molecular mechanisms of cysteine modifications | GlcNAc and ADP-ribose Previously: The Francis Crick Institute/Imperial College London (postdoc), University of Dundee (PhD)
The Thermo Fisher situation keeps getting worse. We've now collected 450+ problematic images presented as verification data in TF's antibody catalog. This includes: 🖌️ Dozens more images with duplications or painting 🖨️ Hundreds of blots that all share the same background (behold slideshow below)
Happy to share the final version of this work is now out in @natchembio.nature.com. Lots of additional exciting data! Congrats to all the authors!
Posttranslational modifications remodel proteome-wide ligandability - Nature Chemical Biology
A chemoproteomic strategy reveals how posttranslational modifications reshape protein ligandability across the human proteome, uncovering more than 400 state-dependent interactions, including phosphor...
nature.com
Chris Parker@chrisgparker.bsky.social · last yr.Excited to share a new preprint from the lab. We show that PTMs like phosphorylation & glycosylation dynamically reshape proteome-wide ligandability in cells, including proteins like KRAS. Great collaboration with the Huang Lab, @forlilab.bsky.social and BMS. www.biorxiv.org/content/10.1...
Fascinating findings by using a clever technique!
Komander Lab@komanderlab.bsky.social · 5mo agoCheck out our latest paper on the ubiquitination of glycogen in cells and tissues! Congratulations to Marco Jochem (@marcojochem.bsky.social) and Simon Cobbold for leading this study and to collaborators @craigagoodman1.bsky.social, @pgregorevic.bsky.social, Kai Hofmann and Thomas Hermanns.
Just two more days to submit abstracts for the "PARP Family and ADP-ribosylation CSHL meeting. We have an amazing lineup of speakers. The majority of speakers are selected from abstracts. Don't miss out! meetings.cshl.edu/meetings.asp...
The PARP Family & ADP-ribosylation
Cold Spring Harbor Laboratory Meetings & Courses -- a private, non-profit institution with research programs in cancer, neuroscience, plant biology, genomics, bioinformatics.
meetings.cshl.edu
New year, new preprint! 🎊 We are excited to share our recent work on #E3 ligase regulation in #metabolism! www.biorxiv.org/content/10.6... #ubiquitin #targetedproteindegradation #chemicalbiology 1/6
A CK2-FBXW11 kinase-E3 ubiquitin ligase cascade is a metabolic sensor regulating Tryptophan 2,3-dioxygenase stability
Small molecules toggling the ubiquitin-proteasome system (UPS) are powerful regulators of protein degradation. Yet, mechanistic knowledge of how endogenous ligands gate UPS decisions remains rudimentary. Here, we define control of UPS access to Tryptophan-2,3-dioxygenase (TDO2), which converts the essential amino acid tryptophan (Trp) to N-formylkynurenine. When Trp concentrations are limiting, TDO2 is degraded to avert tryptophanemia. Using CRISPRi screening and biochemistry, we identify a CK2-FBXW11 kinase-E3 ligase cascade that generates and recognizes tandem TDO2 phosphodegrons when not protected by Trp. Trp binding to an exosite safeguards TDO2 from phosphorylation-dependent ubiquitylation. Effects of Trp analogs on CK2-FBXW11-dependent ubiquitylation indicated that the indole, amino, and carboxylate groups are necessary for substrate shielding. Cryo-EM reveals how these moieties order a region proximal to the phosphodegrons; without Trp, this segment is flexible, enabling phosphorylation-coupled ubiquitylation. Overall, our data uncovered an endogenous small molecule allosterically stabilizing its own metabolizing enzyme through protection from a phosphorylation-ubiquitylation cascade. ### Competing Interest Statement B.A.S. is a member of the scientific advisory boards of Proxygen and Lyterian. The other authors declare no competing interests. Max Planck Society, https://ror.org/01hhn8329 European Union, ERC AdvG, UPSmeetMet, 101098161 to BAS Boehringer Ingelheim Fonds, https://ror.org/00dkye506
biorxiv.org
Learn more about the interplay between ADP-ribosylation and ubiquitination: PARG regulates proteasomal degradation of the ADP-ribosyl hydrolase TARG1 by preventing PAR-dependent ubiquitination mediated by the E3 ligases HUWE1 and TRIP12 www.sciencedirect.com/science/arti...
PARG regulates the proteasomal degradation of TARG1
ADP-ribosylation (ADPr) is a reversible modification of macromolecules critical for the regulation of genome stability, stress responses, and proteost…
sciencedirect.com
Check out our latest story on AHR and PARP7 (TIPARP) degradation by the ADP-ribose-targeting E3 ligase DTX2 in the first issue of 2026 @embojournal.org! link.springer.com/article/10.1...
Ubiquitin pathway blockade reveals endogenous ADP-ribosylation marking PARP7 and AHR for degradation - The EMBO Journal
ADP-ribosylation is an important protein post-translational modification catalysed by a family of PARP enzymes in humans and is involved in DNA damage and immunity among other processes. While poly-AD...
link.springer.com
Thrilled to share our latest study, led by @reikatei.bsky.social, in @natchembio.nature.com! We began by asking a simple question—how do cells know if they have too much of a lipid in a particular membrane, and how do they respond to rectify this imbalance? www.nature.com/articles/s41... More info 👇
Membrane editing with proximity labeling reveals regulators of lipid homeostasis - Nature Chemical Biology
Coupling an optogenetic lipid-modifying enzyme with proximity labeling reveals protein networks and mechanisms regulating lipid homeostasis in the membranes of target organelles.
nature.com
Is arginine the new cysteine?! Check out our lab's latest in collaboration with @ianseiple.bsky.social's team where we introduce ninhydrin as a selective covalent warhead and probe targeting reactive arginines. www.biorxiv.org/content/10.6...
Ninhydrin as a covalent warhead for chemical proteomic-enabled discovery and selective engagement of reactive arginines
Covalent molecules have emerged as next-generation therapeutics and as powerful tools for perturbing fundamental biological processes. Chemical proteomic methods to screen for reactive proteinaceous a...
biorxiv.org
Online now! Online now! An interactive resource mapping the proteome and reactive cysteine landscape across the NCI-60 reveals cell and tissue-specific profiles #chembiol
An interactive resource mapping the proteome and reactive cysteine landscape across the NCI-60 reveals cell and tissue-specific profiles
Montaño et al. generate an integrated proteomic and cysteine reactivity resource for the NCI-60 cancer cell line panel, offering quantitative data on over 12,000 proteins and 36,000 cysteines to enable future studies on protein function, cysteine biology, and covalent drug discovery.
dlvr.it
I have a PhD position available with start date September 2026 at the University of Manchester. Proteomics analysis of flow cytometry-based isolated pathogen-containing phagosomes Due to funding requirements, this position is for UK home students only. www.findaphd.com/phds/project...
Proteomics analysis of flow cytometry-based isolated pathogen-containing phagosomes at The University of Manchester on FindAPhD.com
PhD Project - Proteomics analysis of flow cytometry-based isolated pathogen-containing phagosomes at The University of Manchester, listed on FindAPhD.com
findaphd.com
SAVE THE DATE! The EMBO workshop "Ubiquitin and Ubiquitin-like proteins in Health and Disease" will be on September 2026. Exciting line up of talks and an amazing location! Organised by @kulathu.bsky.social, @merbllab.bsky.social, @simonapolo.bsky.social, Claudio Joazeiro. Registration open soon.
Very happy to share our collaborative project on FAM118 proteins - noncanonical sirtuins that form filaments and process NAD in human and other vertebrate cells.
Filament formation and NAD processing by noncanonical human FAM118 sirtuins
Nature Structural & Molecular Biology - Baretić and Missoury et al. identify vertebrate proteins FAM118B and FAM118A as sirtuins similar to bacterial antiphage enzymes and show that...
rdcu.be
Mono-ADP-ribosylation as a degradation mark? @andriigorelik.bsky.social, Ivan Ahel et al observe increased ADP-ribosylation of aryl hydrocarbon receptor (AHR) & PARP7 upon ubiquitin-proteasome blockage, crosstalk with DTX2 E3, as rapid AHR-transcription off-switch www.embopress.org/doi/full/10....
In our latest study we show that ligand-activated transcription factor AHR (environmental sensor) is ADP-ribosylated by PARP7. This ADP-ribose mark is recognised by the E3 ubiquitin ligase DTX2 targeting AHR for proteasomal degradation, enabling cells to rapidly shut down AHR-mediated transcription.
Ubiquitin pathway blockade reveals endogenous ADP-ribosylation marking PARP7 and AHR for degradation | The EMBO Journal
imageimageDegradation mechanisms of transcriptionally active aryl hydrocarbon receptor (AHR) are unclear. This work reveals that PARP7 ADP-ribosylates itself and ligand-bound AHR, creating a recogniti...
embopress.org
Online now! CBX4 acetoacetylation as an inhibitory mechanism of HIF-1α activity #chembiol
CBX4 acetoacetylation as an inhibitory mechanism of HIF-1α activity
Li et al. identify XZA-1 as a small-molecule activator of HADH that increases acetoacetyl-CoA, inducing CBX4 K106 acetoacetylation. This modification suppresses CBX4 SUMO E3 ligase activity, reduces HIF-1α SUMOylation, and attenuates its transcriptional activity.
dlvr.it
Out in @natcomms.nature.com: Cryo-EM structure of the pseudo-HAT-containing O-GlcNAcase! Especially exciting since multiple companies are developing O-GlcNAcase inhibitors for Alzheimer's disease (tau is O-GlcNAcylated). Glad to have a small contribution in this story. Congrats to all authors!
Multi-domain O-GlcNAcase structures reveal allosteric regulatory mechanisms - Nature Communications
This work reveals how a regulatory domain in O-GlcNAc hydrolase (OGA) shapes enzyme flexibility and activity, uncovering mechanisms that help maintain O-GlcNAc balance in cells.
nature.com
Historically, viruses were thought to primarily use host cell's translational machinery. New work from @harvardcellbio.bsky.social faculty Amy Lee reveals that a giant DNA virus encodes its own IF4F initiation complex, suggesting an unexpected evolutionary innovation. www.biorxiv.org/content/10.1...
Giant DNA viruses encode a hallmark translation initiation complex of eukaryotic life
In contrast to living organisms, viruses were long thought to lack protein synthesis machinery and instead depend on host factors to translate viral transcripts. Here, we discover that giant DNA virus...
biorxiv.org
New work from our own Chouchani Lab finds that LRRC58 is the substrate adaptor of an E3 ubiquitin ligase that mediates proteasomal degradation of CDO1, the rate-limiting enzyme of the catabolic shunt of cysteine to taurine in response to altered Cysteine levels. www.nature.com/articles/s41...
Covariation MS uncovers a protein that controls cysteine catabolism - Nature
A mass spectrometry-based approach globally identifies protein regulators of metabolism and reveals the role of LRRC58 in controlling cysteine catabolism.
nature.com
Robert Redford (RIP) survived a childhood bout of polio though bedridden for 2 weeks In 2014, he directed a short film on the architecture and mission of La Jolla's Salk Institute—honoring founder Jonas Salk, inventor of the polio vaccine that has saved countless lives, and architect Louis Kahn
CATHEDRALS OF CULTURE - Clip ROBERT REDFORD: Salk Institute -- La Jolla, California, USA - HD
YouTube video by neueroadmovies
youtu.be
A few years back we discovered a dual hybrid protein modification composed of an ADP-ribose dinucleotide and the ubiquitin moieties (ADPr-Ub). Here you can read our review that will give you an update on this increasingly popular topic: rdcu.be/eETIT
The rise of ADP-ribose–ubiquitin
Nature Structural & Molecular Biology - Post-translational modifications show mechanistic crosstalk, exemplified by the ADP-ribose–ubiquitin hybrid signal, in which one post-translational...
rdcu.be
Delighted to share our work on cellular ubiquitination of drug-like compounds by HUWE1 - a surprising journey! Kudos to all contributors & first authors, Barbara Orth and Pavel Pohl. Sincere thanks to @ireserra.bsky.social #NatCommun for expertly guiding the winding publishing path. rdcu.be/eDzPk
Selective ubiquitination of drug-like small molecules by the ubiquitin ligase HUWE1
Nature Communications - Ubiquitination is a versatile modification system in eukaryotic cells. Here, the authors unveil that the ubiquitin ligase HUWE1 can modify drug-like small-molecule...
rdcu.be
Are you a postdoc interested in the mechanisms of disease? Do you have a great record and an exciting vision? Come and start your own lab @dunnschool.bsky.social by applying for sponsorship for early career fellowships. Deadline 30th September...pass it on! www.path.ox.ac.uk/work-with-us...
Group Leader Career Development Fellowships - Dunn School
Are you an early career researcher interested in the cell or molecular mechanisms underlying disease? Do you have an outstanding record and an innovative research plan?
path.ox.ac.uk
Happy to share that my first-author paper from my postdoc at Imperial @imperialcollegeldn.bsky.social and The Francis Crick Institute @crick.ac.uk is now published in Cell Reports! www.sciencedirect.com/science/arti...
MYC deregulation sensitizes cancer cells to N-myristoyltransferase inhibition
Human N-myristoyltransferases (NMTs) catalyze N-terminal protein N-myristoylation and are promising targets in cancer, with an emerging mechanistic ra…
sciencedirect.com
Want to know how lipidation of some nascent chains takes place by NMT2-- Check our latest work on how NAC couples Protein Synthesis with Nascent Polypeptide Myristoylation on the Ribosome out today @embojournal.org: www.embopress.org/doi/full/10....
Excited to share a new preprint from the lab. We show that PTMs like phosphorylation & glycosylation dynamically reshape proteome-wide ligandability in cells, including proteins like KRAS. Great collaboration with the Huang Lab, @forlilab.bsky.social and BMS. www.biorxiv.org/content/10.1...
Post-Translational Modifications Remodel Proteome-Wide Ligandability
Post-translational modifications (PTMs) vastly expand the diversity of human proteome, dynamically reshaping protein activity, interactions, and localization in response to environmental, pharmacologi...
biorxiv.org
I still can’t believe that all NIH grants to my colleagues at Harvard and Harvard Medical School have been nullified. And that, as a nation, we’re somehow okay with this illegal, arbitrary, and petty act. Just think of the consequences: scientists, students, and patients will all suffer.
A few years back we discovered a dual hybrid protein modification composed of ADP-ribose dinucleotide and ubiquitin (ADPr-Ub). Now we reveal that ADPr-Ub can be further ubiquitinated by the E3 ubiquitin ligase RNF114! www.nature.com/articles/s41... www.science.org/doi/10.1126/...
Identification of RNF114 as ADPr-Ub reader through non-hydrolysable ubiquitinated ADP-ribose - Nature Communications
Deltex E3s modify ADP-ribosylated targets with ubiquitin, creating a hybrid modification whose readers remains unknown. Here, the authors synthesise a non-hydrolysable probe that mimics the modificati...
nature.com
An amazing paper from van der Heden and Ahel groups! They use clever chemistry to identify RNF114 as a dual ADP-ribose-Ubiquitin reader involved in the DNA damage response! Congratulations to first authors Max, @chatrin-c.bsky.social and Rishov. Happy to have a small contribution in this story
Identification of RNF114 as ADPr-Ub reader through non-hydrolysable ubiquitinated ADP-ribose - Nature Communications
Deltex E3s modify ADP-ribosylated targets with ubiquitin, creating a hybrid modification whose readers remains unknown. Here, the authors synthesise a non-hydrolysable probe that mimics the modificati...
nature.com
This is wild! Engineering E. coli bacteria to turn plastic waste into paracetamol (Tylenol) www.nature.com/articles/s41... www.nature.com/articles/s41...
