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Reposted by Jakob Farnung

Lucas Farnung @lucas.farnunglab.com · Aug 29

🧬 Transcription elongation by RNA polymerase II relies on a web of elongation factors. Our new work shows how IWS1 acts as a modular scaffold to stabilize & stimulate elongation. Fantastic work by Della Syau! www.biorxiv.org/content/10.1...

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Reposted by Jakob Farnung

Carolin Klose @carolinklose.bsky.social · Aug 5

Excited to share our latest study in @natcomms.nature.com , where we characterize the chaperone function of the ER membrane protein complex (EMC)—supporting membrane protein biogenesis beyond insertion!
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www.nature.com/articles/s41...

The EMC acts as a chaperone for membrane proteins - Nature Communications

Membrane proteins are essential for any cell but difficult to fold. Here, the authors show that the EMC acts as a chaperone for membrane proteins. They dissect client recognition and provide a molecul...

www.nature.com

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Reposted by Jakob Farnung

Leo Kiss @leokiss.bsky.social · Jun 25

Excited about #ubiquitin and #TPD ?
Then join us tomorrow for the latest instalment of the @danafarber.bsky.social ‬ Targeted Protein Degradation Webinar where Kimberly Stegmaier and I will present our latest work.
dfci.zoom.us/webinar/regi...

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Reposted by Jakob Farnung

Harvard Med Cell Biology @harvardcellbio.bsky.social · Jun 18

Congratulations to our own Lucas Farnung @lucas.farnunglab.com who has been named as one of 30 Freeman Hrabowski Scholars for 2025 by the Howard Hughes Medical Institute (HHMI). So well deserved deserved !! www.hhmi.org/programs/fre...

The 2025 Freeman Hrabowski Scholars | HHMI

Freeman Hrabowski Scholars are outstanding early career faculty who have the potential to become leaders in their research fields.

www.hhmi.org

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Reposted by Jakob Farnung

Leo Kiss @leokiss.bsky.social · Jun 2

Schulman lab is ready for the GRK2243 Symposium: Understanding ubiquitination: from molecular mechanisms to disease in würzburg

#wUeBI2025 @grk2243.bsky.social
@jakobfarnung.bsky.social @samuelmaiwald.bsky.social @hannahbkmpr.bsky.social

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Jakob Farnung @jakobfarnung.bsky.social · May 26

Super cool story on branched UB chain formation. Congrats Sam!

Samuel Maiwald @samuelmaiwald.bsky.social · May 26

Excited to share our latest study on how K29/K48-branched #ubiquitin chains are forged by the #E3 ligase TRIP12, and how this suggests a consensus mechanism for chain formation by HECT E3s!

@natsmb.nature.com

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www.nature.com/articles/s41...

TRIP12 structures reveal HECT E3 formation of K29 linkages and branched ubiquitin chains - Nature Structural & Molecular Biology

Using biochemistry, chemical biology, and cryo-EM, Maiwald et al. elucidate how TRIP12 forms K29 linkages and K29/K48-linked branched ubiquitin chains, revealing a mechanism for polyubiquitylation sha...

www.nature.com

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Reposted by Jakob Farnung

Samuel Maiwald @samuelmaiwald.bsky.social · May 26

Excited to share our latest study on how K29/K48-branched #ubiquitin chains are forged by the #E3 ligase TRIP12, and how this suggests a consensus mechanism for chain formation by HECT E3s!

@natsmb.nature.com

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www.nature.com/articles/s41...

TRIP12 structures reveal HECT E3 formation of K29 linkages and branched ubiquitin chains - Nature Structural & Molecular Biology

Using biochemistry, chemical biology, and cryo-EM, Maiwald et al. elucidate how TRIP12 forms K29 linkages and K29/K48-linked branched ubiquitin chains, revealing a mechanism for polyubiquitylation sha...

www.nature.com

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Reposted by Jakob Farnung

Lucas Farnung @lucas.farnunglab.com · May 6

🧬🎉Thrilled to share our new chromatin remodeling study! We reveal three states of human CHD1 and identify a novel "anchor element" that interacts with the acidic patch—conserved among remodelers. Our structures clarify mechanisms of remodeler recruitment! Link: authors.elsevier.com/a/1l2ik3vVUP...

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Reposted by Jakob Farnung

Haselbach Lab @haselbachlab.bsky.social · Apr 9

New Preprint: We have solved the structure of the proteasome in complex with two different ubiquitin chains: www.biorxiv.org/content/10.1... This work is spearheaded by PhD Student Sascha Amann
Let me walk you through it 🧵 1/9

Structural basis for the ubiquitin chain recognition of the human 26S proteasome

Proteasomal degradation is a fundamental process for all eukaryotic life. A protein destined for degradation is first tagged with a polyubiquitin chain, which is selected by the proteasome. Different ...

www.biorxiv.org

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Jakob Farnung @jakobfarnung.bsky.social · Mar 24

If you are interested in Ubiquitin this paper is a must read! Congrats Leo!

Leo Kiss @leokiss.bsky.social · Mar 24

Super excited to share our latest work on deciphering the #Ubiquitin Code

“𝗨𝗯𝗶𝗥𝗘𝗔𝗗 𝗱𝗲𝗰𝗶𝗽𝗵𝗲𝗿𝘀 𝗽𝗿𝗼𝘁𝗲𝗮𝘀𝗼𝗺𝗮𝗹 𝗱𝗲𝗴𝗿𝗮𝗱𝗮𝘁𝗶𝗼𝗻 𝗰𝗼𝗱𝗲 𝗼𝗳 𝗵𝗼𝗺𝗼𝘁𝘆𝗽𝗶𝗰 𝗮𝗻𝗱 𝗯𝗿𝗮𝗻𝗰𝗵𝗲𝗱 𝗞48 𝗮𝗻𝗱 𝗞63 𝘂𝗯𝗶𝗾𝘂𝗶𝘁𝗶𝗻 𝗰𝗵𝗮𝗶𝗻𝘀”

@cp-molcell.bsky.social

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www.cell.com/molecular-ce...

UbiREAD deciphers proteasomal degradation code of homotypic and branched K48 and K63 ubiquitin chains

Ubiquitin chains determine the fates of their modified proteins, including proteasomal degradation. Kiss et al. present UbiREAD, a technology to monitor cellular degradation and deubiquitination at hi...

www.cell.com

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Reposted by Jakob Farnung

jeffreybode.bsky.social @jeffreybode.bsky.social · Feb 12

It's finally out – actually out and in print! Many thanks to @jcornlab.bsky.social @matthiasmuhar.bsky.social @jakobfarnung.bsky.social and all the fantastic collaborators. What started as pure curiosity lead to an amazing find!

www.nature.com/articles/s41...

C-terminal amides mark proteins for degradation via SCF–FBXO31 - Nature

SCF–FBXO31 scans proteins for C-terminal amidation and marks them for subsequent proteasomal degradation.

www.nature.com

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Reposted by Jakob Farnung

Brian Liau @brianliau.bsky.social · Feb 12

Today in @nature.com we share our back-to-back stories with Ning Zheng’s lab revealing chemical-genetic convergence between a molecular glue degrader & E3 ligase cancer mutations. 1/5

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Reposted by Jakob Farnung

Lucas Farnung @lucas.farnunglab.com · Jan 31

Excited about mechanistic biology and processes in the cell's nucleus? Join our lab as a post-doctoral researcher! We have a state-of-the-art cryo-EM facility (new microscopes coming!), a brand-new lab space, and a vibrant community at HMS!
DM/email me or check farnunglab.com for more info.

Farnung Lab

farnunglab.com

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Reposted by Jakob Farnung

Lucas Farnung @lucas.farnunglab.com · Jan 30

Our story on the mechanism of co-transcriptional histone mark deposition is now officially out: www.science.org/doi/10.1126/...

Structural basis of H3K36 trimethylation by SETD2 during chromatin transcription

During transcription, RNA polymerase II traverses through chromatin, and posttranslational modifications including histone methylations mark regions of active transcription. Histone protein H3 lysine ...

www.science.org

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Reposted by Jakob Farnung

Jacob Corn @jcornlab.bsky.social · Jan 30

Cells are filled with toxic stuff that damages healthy proteins. Is that garbage just left to rot on the curb? No way! Ubiquitin ligases have evolved to recognize chemical damage and clean it up! www.nature.com/articles/s41...

C-terminal amides mark proteins for degradation via SCF–FBXO31 - Nature

SCF–FBXO31 scans proteins for C-terminal amidation and marks them for subsequent proteasomal degradation.

www.nature.com

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Reposted by Jakob Farnung

Clausen Lab @clausenlab.bsky.social · Jan 29

scary but fascinating - cells have a degradation pathway that hunts down C-terminal scars (amides!) on damaged proteins. just wow. chemical biology plus CRISPR at its best. big congrats to all authors!

www.nature.com/articles/s41...

C-terminal amides mark proteins for degradation via SCF–FBXO31 - Nature

SCF–FBXO31 scans proteins for C-terminal amidation and marks them for subsequent proteasomal degradation.

www.nature.com

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Reposted by Jakob Farnung

Micha Rapé Lab @micharapelab.bsky.social · Jan 29

Very excited to highlight @jcornlab's beautiful work on the E3 ligase SCF-FBXO31, which recognizes chemically damaged proteins. Mutations in FBXO31 cause disease by substrate-rewiring, really cool. Congratulations to all authors!

rdcu.be/d7WGc

Signs of damage that drive protein degradation | Nature

Many environmental toxins damage proteins, which then must be removed to avoid dangerous protein aggregation and disease. How cells dispose of chemically modified proteins has been unclear, but a discovery offers some clues. How the stress-response machinery eliminates damaged proteins.

rdcu.be

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Reposted by Jakob Farnung

Leo Kiss @leokiss.bsky.social · Jan 29

Super exiting new work revealing a novel quality control pathway for c-terminal amides!

Jakob Farnung @jakobfarnung.bsky.social · Jan 29

🎉Super excited to share our story on how the substrate receptor FBXO31 functions as a quality control factor by recognizing amides. This has been an amazing collaboration between Bode lab and @jcornlab.bsky.social. Special shutout goes to @matthiasmuhar.bsky.social www.nature.com/articles/s41...

C-terminal amides mark proteins for degradation via SCF–FBXO31 - Nature

SCF–FBXO31 scans proteins for C-terminal amidation and marks them for subsequent proteasomal degradation.

www.nature.com

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Reposted by Jakob Farnung

Thomas Arnesen @natmachinery.bsky.social · Jan 29

On the degradation of damaged cellular proteins via C-terminal amidation. By Alfred Freeberg & @micharapelab.bsky.social. @ispt-proteinterm.bsky.social www.nature.com/articles/d41...

Signs of damage that drive protein degradation

How the stress-response machinery eliminates damaged proteins.

www.nature.com

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Jakob Farnung @jakobfarnung.bsky.social · Jan 29

And check out a News & Views written by @alfredfreeberg.bsky.social and @micharapelab.bsky.social for highlighting our work. Thank you!

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Jakob Farnung @jakobfarnung.bsky.social · Jan 29

This project really has been a great journey that was only possible by combining chemical and biological expertise. Special thanks also goes out to Raphael Hofmann who started this project with @matthiasmuhar.bsky.social!

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Jakob Farnung @jakobfarnung.bsky.social · Jan 29

Since our preprint we have added exciting new data in collaboration with the Schulman lab @mpibiochem.bsky.social, @martinjinek.bsky.social and Jessberger lab that further underpin the quality control function of FBXO31.

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Jakob Farnung @jakobfarnung.bsky.social · Jan 29

Using a genome-wide CRISPR screen we identified the SCF-component FBXO31 as a selective reader of C-terminal amides. FBXO31 is a quality control factor, agnostically recognizing any amidated C-terminal amino acid. We propose that oxidative stress can cause spontaneous fragmentation of the peptide-backbone to leading to formation of C-terminally amidated proteins (CTAP).

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Jakob Farnung @jakobfarnung.bsky.social · Jan 29

We combined chemical biology and genetic tools to devise a cellular screening platform to identify modified amino acid degrons (MAAD) that induce protein degradation. Surprisingly the smallest possible change from C-terminal carboxylic acid to an amide induces efficient degradation.

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Jakob Farnung @jakobfarnung.bsky.social · Jan 29

🎉Super excited to share our story on how the substrate receptor FBXO31 functions as a quality control factor by recognizing amides. This has been an amazing collaboration between Bode lab and @jcornlab.bsky.social. Special shutout goes to @matthiasmuhar.bsky.social www.nature.com/articles/s41...

C-terminal amides mark proteins for degradation via SCF–FBXO31 - Nature

SCF–FBXO31 scans proteins for C-terminal amidation and marks them for subsequent proteasomal degradation.

www.nature.com

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