Ekampreet Singh (@esingh) Bsky

The E3 ubiquitin ligase mechanism specifying target-directed microRNA degradation (TDMD) is now published! 🎉🍾 We, @bartellab.bsky.social and Schulman lab, describe how 2-RNA factors control protein degradation by recruiting an E3 ligase. @mpibiochem.bsky.social
www.nature.com/articles/s41...

1 month ago 83 38 1 3

Kiss-intro IMPRS-LM stands for International Max Planck Research School for Living Matter. We are interested in the molecular, chemical and physical properties

You are passionate about ubiquitin, proteostasis and cellular biochemistry and want to be part of a collaborative, ambitious, excited and fun team? I am recruiting PhD students via the @imprs-lm.bsky.social graduate school:
www.imprs-lm.mpg.de/index.php/le...
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1 month ago 15 10 1 0

Formation & function of #MembranelessOrganelles! #CryoET structures of #proteasome storage granules inside cells!
Read our paper @cp-cell.bsky.social!

❕Publication: doi.org/10.1016/j.ce...
❕Press Release: www.biochem.mpg.de/en/pressroom

@uoftmedicine.bsky.social
@erc.europa.eu #UPSmeetMet

2 months ago 71 26 0 2

Amazing work by an amazing labmate! Congratulations @alinathielen.bsky.social on this wonderful study ✨

3 months ago 4 0 0 0

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

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

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3 months ago 43 17 1 5

When RNA Degradation 🤝 meets 🤝 Protein Degradation! tinyurl.com/E3TDMD In a collaboration of @bartellab.bsky.social and Schulman lab, we show that, in target-directed microRNA degradation (TDMD), 2-RNA-factors recruit an E3 ligase and induce the degradation of not only a protein but also RNA (1/5).

3 months ago 117 50 1 4

Cysteine availability tunes ubiquitin signaling via inverse stability of LRRC58 E3 ligase and its substrate CDO1 www.biorxiv.org/content/10.1101/2025.11....

5 months ago 8 6 0 0

Congratulations Caro!! ✨

8 months ago 0 0 0 0

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...

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...

8 months ago 27 9 1 3

Congratulations @samuelmaiwald.bsky.social on this wonderful story about ub chain formation. A must read! ✨

10 months ago 2 0 0 0

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...

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...

10 months ago 44 17 4 3

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...

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...

1 year ago 131 44 16 4

Posts by Ekampreet Singh