Reprograming of the ubiquitin ligase Ubr1 by intrinsically disordered Roq1 through cooperating multifunctional motifs DOI Creative Commons
Niklas Peters,

Sibylle Kanngießer,

Oliver Pajonk

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 24, 2024

One way cells control the speed and specificity of protein degradation is by regulating activity ubiquitin ligases. Upon proteotoxic stress in yeast, intrinsically disordered Roq1 binds ligase Ubr1 as a pseudosubstrate, thereby modulating substrates N-degron pathway promoting elimination misfolded proteins. The mechanism underlying this reprograming unknown. Here, we show that controls means two cooperating multifunctional motifs. N-terminal arginine short hydrophobic motif interact with part heterobivalent binding mechanism. Via its arginine, regulates ubiquitination various folded motif, accelerates These findings reveal how small, simple architecture engages parallel channels communication to reprogram functionally complex ligase.

Язык: Английский

mTORC1 regulates the pyrimidine salvage pathway by controlling UCK2 turnover via the CTLH-WDR26 E3 ligase DOI Creative Commons
Brittany Q Pham, Sang Ah Yi, Alban Ordureau

и другие.

Cell Reports, Год журнала: 2025, Номер 44(1), С. 115179 - 115179

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
Reprograming of the ubiquitin ligase Ubr1 by intrinsically disordered Roq1 through cooperating multifunctional motifs DOI Creative Commons
Niklas Peters,

Sibylle Kanngießer,

Oliver Pajonk

и другие.

The EMBO Journal, Год журнала: 2025, Номер unknown

Опубликована: Фев. 7, 2025

Язык: Английский

Процитировано

1
Muskelin is a substrate adaptor of the highly regulated Drosophila embryonic CTLH E3 ligase DOI Creative Commons
Chloe A. Briney, Jesslyn C. Henriksen,

Chien-Chen Lin

и другие.

EMBO Reports, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

Abstract The maternal-to-zygotic transition (MZT) is a conserved developmental process where the maternally-derived protein and mRNA cache replaced with newly made zygotic gene products. We have previously shown that in Drosophila deposited RNA-binding proteins ME31B, Cup, Trailer Hitch are ubiquitylated by CTLH E3 ligase cleared. However, organization regulation of complex remain poorly understood flies because lacks an identifiable substrate adaptor, mechanisms restricting degradation ME31B its cofactors to MZT unknown. Here, we show multi-pronged, including transcriptional control OVO autoinhibition ligase. One major regulatory target subunit Muskelin, which demonstrate adaptor for complex. Finally, find Muskelin has few targets beyond three known proteins, showing exquisite specificity. Thus, multiple levels integrated restrict activity embryonic early embryogenesis, during time it regulates important proteins.

Язык: Английский

Процитировано

0
Design of PROTACs utilizing the E3 ligase GID4 for targeted protein degradation DOI
Yanran Li, Kaiwen Bao, Jing Sun

и другие.

Nature Structural & Molecular Biology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 28, 2025

Язык: Английский

Процитировано

0
Pooled endogenous protein tagging and recruitment for systematic profiling of protein function DOI Creative Commons
Yevgeniy V. Serebrenik,

Deepak Mani,

Timothé Maujean

и другие.

Cell Genomics, Год журнала: 2024, Номер unknown, С. 100651 - 100651

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

3
RANBP9 and RANBP10 cooperate in regulating non-small cell lung cancer proliferation DOI Creative Commons
Arturo Orlacchio, Yasuko Kajimura, Lara Rizzotto

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

Abstract Background RANBP9 and RANBP10, also called Scorpins, are essential components of the C-terminal to LisH (CTLH) complex, an evolutionarily conserved poorly investigated multisubunit E3 ligase. Their role in non-small cell lung cancer (NSCLC) is unknown. Methods In this study, first we used stable loss-of function overexpression inducible lines investigate ability either or RANBP10 form their own functional CTLH complex. Then, probed lysates from patient tumors analyzed data publicly available repositories expression RANBP10. Finally, vitro recapitulate observed patients changes proteome ubiquitylome associated with NSCLC. Results Here, show that two Scorpins both expressed NSCLC cells them can independently support formation Short-term experiments revealed proteins balance each other terms expression, acute one results significant reshaping ubiquitylome. A higher RANBP9/RANBP10 ratio greater proliferation patients. Acute increased slows decreases level proliferation-associated proteins, including key players DNA replication. Conclusions We present evidence act as partial antagonists work together sophisticated rheostat modulate complex ubiquitylation output, which regulates biological processes These suggest be considered targets for treatment

Язык: Английский

Процитировано

0
The hGIDGID4E3 ubiquitin ligase complex targets ARHGAP11A to regulate cell migration DOI Creative Commons
Halil Bagci, Martin Winkler, Benjamin Grädel

и другие.

Life Science Alliance, Год журнала: 2024, Номер 7(12), С. e202403046 - e202403046

Опубликована: Окт. 10, 2024

The human CTLH/GID (hGID) complex emerged as an important E3 ligase regulating multiple cellular processes, including cell cycle progression and metabolism. However, the range of biological functions controlled by hGID remains unexplored. Here, we used proximity-dependent biotinylation (BioID2) to identify proteins interacting with complex, among them, substrate candidates that bind GID4 in a pocket-dependent manner. Biochemical assays revealed binds ubiquitinates ARHGAP11A, thereby targeting this RhoGAP for proteasomal degradation. Indeed, depletion or impeding binding pocket PFI-7 inhibitor stabilizes ARHGAP11A protein amounts, although it carries no functional N-terminal degron. Interestingly, inactivation impairs motility directed movement increasing levels at periphery, where inactivates RhoA. Together, identified wide substrates uncovered unique function migration ARHGAP11A.

Язык: Английский

Процитировано

2
Interplay between β-propeller subunits WDR26 and muskelin regulates the CTLH E3 ligase supramolecular complex DOI Creative Commons
Matthew E. R. Maitland,

Gabriel Onea,

Dominic D. G. Owens

и другие.

Communications Biology, Год журнала: 2024, Номер 7(1)

Опубликована: Дек. 19, 2024

The Pro/N-degron recognizing C-terminal to LisH (CTLH) complex is an E3 ligase of emerging interest in the developmental biology field and for targeted protein degradation (TPD) modalities. human CTLH forms distinct supramolecular ring-shaped structures dependent on multimerization WDR26 or muskelin β-propeller proteins. Here, we find that, HeLa cells, activity dictated by interplay between tandem with autoregulation. Proteomic experiments revealed that complex-associated turnover a major ubiquitin-mediated event unstimulated cells. We observed binding scaffold interchangeable, indicative formation separate complexes, which correlated proteomes knockout found mTOR inhibition-induced containing HMGCS1 distinctly regulated muskelin-specific complex. Finally, inhibition also activated degradation, likely as autoregulatory feedback mechanism regulate activity. Thus, rather than swapping substrate receptors, controls selectivity through differential association its oligomeric subunits muskelin. mediate two complexes have different targets. Inhibition signalling regulates cells leads

Язык: Английский

Процитировано

1
Muskelin acts as a substrate receptor of the highly regulated Drosophila CTLH E3 ligase during the maternal-to-zygotic transition DOI
Chloe A. Briney, Jesslyn C. Henriksen, Chenwei Lin

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 1, 2024

The maternal-to-zygotic transition (MZT) is a conserved developmental process where the maternally-derived protein and mRNA cache replaced with newly made zygotic gene products. We have previously shown that in

Язык: Английский

Процитировано

0
Reprograming of the ubiquitin ligase Ubr1 by intrinsically disordered Roq1 through cooperating multifunctional motifs DOI Creative Commons
Niklas Peters,

Sibylle Kanngießer,

Oliver Pajonk

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 24, 2024

One way cells control the speed and specificity of protein degradation is by regulating activity ubiquitin ligases. Upon proteotoxic stress in yeast, intrinsically disordered Roq1 binds ligase Ubr1 as a pseudosubstrate, thereby modulating substrates N-degron pathway promoting elimination misfolded proteins. The mechanism underlying this reprograming unknown. Here, we show that controls means two cooperating multifunctional motifs. N-terminal arginine short hydrophobic motif interact with part heterobivalent binding mechanism. Via its arginine, regulates ubiquitination various folded motif, accelerates These findings reveal how small, simple architecture engages parallel channels communication to reprogram functionally complex ligase.

Язык: Английский

Процитировано

0