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
1/7
www.nature.com/articles/s41...
@natsmb.nature.com
1/7
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
May 26, 2025 at 9:37 AM
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
1/7
www.nature.com/articles/s41...
@natsmb.nature.com
1/7
www.nature.com/articles/s41...
Excited to report our discovery of an important component of the oxidative stress response: the E3 ligase TRIP12. It acts as a chain elongation factor that amplifies CUL3-KEAP1 activity to drive NRF2 degradation as cells recover from stress.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12
The oxidative stress response is centered on the transcription factor NRF2 and protects cells from reactive oxygen species (ROS). While ROS inhibit the E3 ligase CUL3-KEAP1 to stabilize NRF2 and elici...
www.biorxiv.org
November 26, 2024 at 2:53 PM
Excited to report our discovery of an important component of the oxidative stress response: the E3 ligase TRIP12. It acts as a chain elongation factor that amplifies CUL3-KEAP1 activity to drive NRF2 degradation as cells recover from stress.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Amazing new story from Michael Rape’s lab @ucberkeleyofficial.bsky.social on dynamic regulation of the oxidative stress response by the E3 ligase TRIP12!
Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12 https://www.biorxiv.org/content/10.1101/2024.11.25.625235v1
Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12 https://www.biorxiv.org/content/10.1101/2024.11.25.625235v1
The oxidative stress response is centered on the transcription factor NRF2 and protects cells from r
www.biorxiv.org
November 26, 2024 at 5:02 PM
Amazing new story from Michael Rape’s lab @ucberkeleyofficial.bsky.social on dynamic regulation of the oxidative stress response by the E3 ligase TRIP12!
Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12 https://www.biorxiv.org/content/10.1101/2024.11.25.625235v1
Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12 https://www.biorxiv.org/content/10.1101/2024.11.25.625235v1
The oxidative stress response is centered on the transcription factor NRF2 and protects cells from r
www.biorxiv.org
November 26, 2024 at 3:46 AM
Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12 https://www.biorxiv.org/content/10.1101/2024.11.25.625235v1
New online: TRIP12 structures reveal HECT E3 formation of K29 linkages and branched ubiquitin chains
TRIP12 structures reveal HECT E3 formation of K29 linkages and branched ubiquitin chains
Nature Structural & Molecular Biology, Published online: 26 May 2025; doi:10.1038/s41594-025-01561-1Using 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 shared by some HECT E3s.
go.nature.com
May 26, 2025 at 11:48 AM
New online: TRIP12 structures reveal HECT E3 formation of K29 linkages and branched ubiquitin chains
Thrilled to share how proteomic analysis led to the discovery of "TRIP12’s role in the governance of DNA polymerase β involvement in DNA damage response and repair" url: academic.oup.com/nar/article/... @ianywonglab.bsky.social @weldeiry.bsky.social @emgsus.bsky.social
TRIP12’s role in the governance of DNA polymerase β involvement in DNA damage response and repair
Abstract. The multitude of DNA lesion types, and the nuclear dynamic context in which they occur, presents a challenge for genome integrity maintenance as
academic.oup.com
July 6, 2025 at 12:46 PM
Thrilled to share how proteomic analysis led to the discovery of "TRIP12’s role in the governance of DNA polymerase β involvement in DNA damage response and repair" url: academic.oup.com/nar/article/... @ianywonglab.bsky.social @weldeiry.bsky.social @emgsus.bsky.social
TRIP12 adds K29-linked ubiquitin onto K48-linked ubiquitin chains. We show that TRIP12 preferentially modifies the proximal ubiquitin to form branched chains.
2/7
2/7
May 26, 2025 at 9:37 AM
TRIP12 adds K29-linked ubiquitin onto K48-linked ubiquitin chains. We show that TRIP12 preferentially modifies the proximal ubiquitin to form branched chains.
2/7
2/7
Excited that our study identifying TRIP12 - an essential E3 ligase mutated in a neurodevelopmental disease - as a critical component of the oxidative stress response is now online. Congratulations to Andrew, Devlon and Jenny! @ucberkeleyofficial.bsky.social
www.sciencedirect.com/science/arti...
www.sciencedirect.com/science/arti...
Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12
Centered on the transcription factor NRF2 and its E3 ligase CUL3KEAP1, the oxidative stress response protects cells from damage by reactive oxygen spe…
www.sciencedirect.com
September 11, 2025 at 2:03 PM
Excited that our study identifying TRIP12 - an essential E3 ligase mutated in a neurodevelopmental disease - as a critical component of the oxidative stress response is now online. Congratulations to Andrew, Devlon and Jenny! @ucberkeleyofficial.bsky.social
www.sciencedirect.com/science/arti...
www.sciencedirect.com/science/arti...
Branched ubiquitin chains are both very interesting and somewhat lagging behind in how well we understand them. Insightful work by @samuelmaiwald.bsky.social from the lab of Brenda Schulman now out @nature.smb@nature.com delineating a key player, TRIP12. 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
May 27, 2025 at 12:53 PM
Branched ubiquitin chains are both very interesting and somewhat lagging behind in how well we understand them. Insightful work by @samuelmaiwald.bsky.social from the lab of Brenda Schulman now out @nature.smb@nature.com delineating a key player, TRIP12. www.nature.com/articles/s41...
Check out our latest study @natsmb.nature.com: Establishing a consensus model for #ubiquitin chain assembly by HECT #E3 ligases: #cryoEM structures of #TRIP12 forming K29-linked and K29/K48-branched chains!
❕ www.nature.com/articles/s41...
@samuelmaiwald.bsky.social @unileiden.bsky.social
❕ www.nature.com/articles/s41...
@samuelmaiwald.bsky.social @unileiden.bsky.social
May 26, 2025 at 2:36 PM
Check out our latest study @natsmb.nature.com: Establishing a consensus model for #ubiquitin chain assembly by HECT #E3 ligases: #cryoEM structures of #TRIP12 forming K29-linked and K29/K48-branched chains!
❕ www.nature.com/articles/s41...
@samuelmaiwald.bsky.social @unileiden.bsky.social
❕ www.nature.com/articles/s41...
@samuelmaiwald.bsky.social @unileiden.bsky.social
O estudo liderado dende a @usc.gal usa modelos de peixe cebra con mutacións do xene TRIP12 para comprender os mecanismos biolóxicos que orixinan algúns trastornos do sistema nervioso.
Investigadores galegos desvelan o papel clave do xene TRIP12 en doenzas raras do neurodesenvolvemento
O estudo liderado dende a USC sitúa o peixe cebra como a clave para comprender os mecanismos biolóxicos que orixinan algúns trastornos
www.gciencia.com
August 20, 2026 at 1:36 PM
O estudo liderado dende a @usc.gal usa modelos de peixe cebra con mutacións do xene TRIP12 para comprender os mecanismos biolóxicos que orixinan algúns trastornos do sistema nervioso.
TRIP12 structures reveal HECT E3 formation of K29 linkages and branched ubiquitin chains pubmed.ncbi.nlm.nih.gov/40419785/ #cryoem
May 27, 2025 at 5:02 PM
TRIP12 structures reveal HECT E3 formation of K29 linkages and branched ubiquitin chains pubmed.ncbi.nlm.nih.gov/40419785/ #cryoem
Roibás-Santos et al. explored, in a zebrafish model, how variations in TRIP12, an intellectual disability-related gene, lead to the pathogenesis of the disease.
Read it at 👉 doi.org/10.1093/brai...
#neuroscience #braincommunications
Read it at 👉 doi.org/10.1093/brai...
#neuroscience #braincommunications
August 26, 2026 at 8:00 AM
Roibás-Santos et al. explored, in a zebrafish model, how variations in TRIP12, an intellectual disability-related gene, lead to the pathogenesis of the disease.
Read it at 👉 doi.org/10.1093/brai...
#neuroscience #braincommunications
Read it at 👉 doi.org/10.1093/brai...
#neuroscience #braincommunications
Amazing chemical biology/structural biology work on K29/K48 branching E3 Ufd4/TRIP12 www.nature.com/articles/s41...
Structural visualization of HECT-type E3 ligase Ufd4 accepting and transferring ubiquitin to form K29/K48-branched polyubiquitination - Nature Communications
The K29/K48 hetero-polyubiquitin signal has been reported to be an enhanced degradation signal, but the enzymatic mechanism of this ubiquitin chain formation is unclear. Here, the authors reveal how t...
www.nature.com
May 10, 2025 at 12:05 PM
Amazing chemical biology/structural biology work on K29/K48 branching E3 Ufd4/TRIP12 www.nature.com/articles/s41...
One TRIP12 side avidly recruits the K48-linked chain, explaining preference for the proximal ubiquitin.
4/7
4/7
May 26, 2025 at 9:37 AM
One TRIP12 side avidly recruits the K48-linked chain, explaining preference for the proximal ubiquitin.
4/7
4/7
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...
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…
www.sciencedirect.com
January 8, 2026 at 8:24 PM
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...
www.sciencedirect.com/science/arti...
Congrats to @rwsobol and colleagues at @BrownUniversity #LegorretaCancerCenter @BrownPathology
TRIP12’s role in the governance of DNA polymerase β involvement in DNA damage response and repair
academic.oup.com/nar/article/...
TRIP12’s role in the governance of DNA polymerase β involvement in DNA damage response and repair
academic.oup.com/nar/article/...
TRIP12’s role in the governance of DNA polymerase β involvement in DNA damage response and repair
Abstract. The multitude of DNA lesion types, and the nuclear dynamic context in which they occur, presents a challenge for genome integrity maintenance as
academic.oup.com
July 6, 2025 at 9:08 PM
Congrats to @rwsobol and colleagues at @BrownUniversity #LegorretaCancerCenter @BrownPathology
TRIP12’s role in the governance of DNA polymerase β involvement in DNA damage response and repair
academic.oup.com/nar/article/...
TRIP12’s role in the governance of DNA polymerase β involvement in DNA damage response and repair
academic.oup.com/nar/article/...
TRIP12 adds K29-linked ubiquitin onto K48-linked ubiquitin chains. We show that TRIP12 preferentially modifies the proximal ubiquitin to form branched chains.
2/7
2/7
May 26, 2025 at 9:21 AM
TRIP12 adds K29-linked ubiquitin onto K48-linked ubiquitin chains. We show that TRIP12 preferentially modifies the proximal ubiquitin to form branched chains.
2/7
2/7
On the other side, acceptor and donor ubiquitins come together with the TRIP12 HECT domain to establish the active site. Both sides cooperate to precisely place K29 of the proximal acceptor ubiquitin for catalysis.
5/7
5/7
May 26, 2025 at 9:37 AM
On the other side, acceptor and donor ubiquitins come together with the TRIP12 HECT domain to establish the active site. Both sides cooperate to precisely place K29 of the proximal acceptor ubiquitin for catalysis.
5/7
5/7
We used activity-based probes to trap TRIP12 in the act of forming a K29/K48-branched triUb and a K29-linked diUb. Visualizing these complexes using cryo-EM revealed TRIP12s catalytic mechanism.
3/7
3/7
May 26, 2025 at 9:37 AM
We used activity-based probes to trap TRIP12 in the act of forming a K29/K48-branched triUb and a K29-linked diUb. Visualizing these complexes using cryo-EM revealed TRIP12s catalytic mechanism.
3/7
3/7
🐠 «O peixe cebra permítenos observar de forma moi precisa como unha alteración xenética afecta o desenvolvemento do organismo desde as súas primeiras fases». Laura Sánchez Piñón, investigadora do @campusterrausc.bsky.social, lidera un estudio pioneiro sobre o xene TRIP12.
www.usc.gal/gl/xornal/no...
www.usc.gal/gl/xornal/no...
Modelos de peixe cebra co xene TRIP12 inactivo achegan claves para comprender diversos trastornos do neurodesenvolvemento | Universidade de Santiago de Compostela
Un equipo da Facultade de Veterinaria da USC, liderado pola profesora Laura Sánchez Piñón e no que participan Maider Roibás-Santos e Andrés Blanco-Hortas, e do Centro Singular de Investigación en Medi...
www.usc.gal
August 20, 2026 at 1:58 PM
🐠 «O peixe cebra permítenos observar de forma moi precisa como unha alteración xenética afecta o desenvolvemento do organismo desde as súas primeiras fases». Laura Sánchez Piñón, investigadora do @campusterrausc.bsky.social, lidera un estudio pioneiro sobre o xene TRIP12.
www.usc.gal/gl/xornal/no...
www.usc.gal/gl/xornal/no...
Check out this amazing paper from @samuelmaiwald.bsky.social! Congrats to all the authors 🎉
#TRIP12 #E3ligases #SchulmanLab
#TRIP12 #E3ligases #SchulmanLab
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
1/7
www.nature.com/articles/s41...
@natsmb.nature.com
1/7
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
May 26, 2025 at 11:15 AM
Check out this amazing paper from @samuelmaiwald.bsky.social! Congrats to all the authors 🎉
#TRIP12 #E3ligases #SchulmanLab
#TRIP12 #E3ligases #SchulmanLab
Combinatorial ubiquitin code degrades deubiquitylation-protected substrates
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Combinatorial ubiquitin code degrades deubiquitylation-protected substrates - Nature Communications
Branched ubiquitin chains promote substrates degradation. Here, the authors describe an interplay between two ubiquitin ligases, K29-linkage-specific TRIP12 and K48-linkage specific UBR5, which assemb...
www.nature.com
March 24, 2025 at 5:15 PM
Combinatorial ubiquitin code degrades deubiquitylation-protected substrates
www.nature.com/articles/s41...
www.nature.com/articles/s41...
One TRIP12 side avidly recruits the K48-linked chain, explaining preference for the proximal ubiquitin.
4/7
4/7
May 26, 2025 at 9:21 AM
One TRIP12 side avidly recruits the K48-linked chain, explaining preference for the proximal ubiquitin.
4/7
4/7
SIRT7 regulates NUCKS1 chromatin binding to elicit metabolic and inflammatory gene expression in senescence and liver aging: Molecular Cell www.cell.com/molecular-ce...
SIRT7 regulates NUCKS1 chromatin binding to elicit metabolic and inflammatory gene expression in senescence and liver aging
Tran et al. determined that the protein deacetylase SIRT7 is degraded during senescence
by the E3 ligase TRIP12. SIRT7 binds to NUCKS1 and, upon SIRT7 loss, NUCKS1 is acetylated
and recruited onto chr...
www.cell.com
June 12, 2025 at 2:55 PM
SIRT7 regulates NUCKS1 chromatin binding to elicit metabolic and inflammatory gene expression in senescence and liver aging: Molecular Cell www.cell.com/molecular-ce...