Evolution, composition and functions of cullin E3 ubiquitin ligases in trypanosomes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F25%3A10515721" target="_blank" >RIV/00216208:11310/25:10515721 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=pftHwLBBZO" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=pftHwLBBZO</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-025-32077-9" target="_blank" >10.1038/s41598-025-32077-9</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Evolution, composition and functions of cullin E3 ubiquitin ligases in trypanosomes

Popis výsledku v původním jazyce

Post-translational modifications (PTMs) modulate protein functions, with ubiquitylation a preeminent example, and playing major roles in protein turnover. Ubiquitylation utilises a ligase enzyme cascade for conjugation of ubiquitin to client proteins, of which there are a large number in humans and lesser numbers in unicellular eukaryotes. The Cullin-RING ligases are amongst the most complex ligase subfamily and are present across the eukaryote lineage. We have reconstructed the evolution of cullin-RING E3 ubiquitin ligases across eukaryotes and experimentally determined the composition of six of seven cullin complexes in trypanosomatids. We find considerable diversity within cullins and reconstruct at least four ancestral pan-eukaryotic subfamilies. Furthermore, we identify expansions of cullin client adaptor protein families, novel client adaptors and demonstrate client specificity in trypanosomatids. We also find evidence for increasing complexity within client adaptors, suggesting ongoing expansion of adapter architecture. Finally, we show that turnover of ornithine decarboxylase (TbODC), an important target of the trypanocide eflornithine, is mediated byTbCul-A/CUL-1. These studies highlight lineage-specific aspects of cullin E3 ligases and their contributions towards eukaryotic complexity.

Název v anglickém jazyce

Evolution, composition and functions of cullin E3 ubiquitin ligases in trypanosomes

Popis výsledku anglicky

Post-translational modifications (PTMs) modulate protein functions, with ubiquitylation a preeminent example, and playing major roles in protein turnover. Ubiquitylation utilises a ligase enzyme cascade for conjugation of ubiquitin to client proteins, of which there are a large number in humans and lesser numbers in unicellular eukaryotes. The Cullin-RING ligases are amongst the most complex ligase subfamily and are present across the eukaryote lineage. We have reconstructed the evolution of cullin-RING E3 ubiquitin ligases across eukaryotes and experimentally determined the composition of six of seven cullin complexes in trypanosomatids. We find considerable diversity within cullins and reconstruct at least four ancestral pan-eukaryotic subfamilies. Furthermore, we identify expansions of cullin client adaptor protein families, novel client adaptors and demonstrate client specificity in trypanosomatids. We also find evidence for increasing complexity within client adaptors, suggesting ongoing expansion of adapter architecture. Finally, we show that turnover of ornithine decarboxylase (TbODC), an important target of the trypanocide eflornithine, is mediated byTbCul-A/CUL-1. These studies highlight lineage-specific aspects of cullin E3 ligases and their contributions towards eukaryotic complexity.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10600 - Biological sciences

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Scientific Reports

ISSN

2045-2322

e-ISSN

2045-2322

Svazek periodika

16

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

18

Strana od-do

2285

Kód UT WoS článku

001665489900001

EID výsledku v databázi Scopus

2-s2.0-105027871819