A stress-responsive p38 signaling axis in choanoflagellates DOI Creative Commons
Florentine U. Rutaganira, Maxwell C. Coyle,

Alex Scopton

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Aug. 27, 2022

Abstract Animal kinases regulate cellular responses to environmental stimuli, including cell differentiation, migration, survival, and response stress, but the ancestry of these functions is poorly understood. Choanoflagellates, closest living relatives animals, encode homologs diverse animal have emerged as model organisms for reconstructing origins. However, efforts study kinase signaling in choanoflagellates been constrained by limitations currently available genetic tools. Here we demonstrate that small molecule approaches provide a complementary scalable approach studying function choanoflagellates. To physiological roles choanoflagellate kinases, established two high-throughput platforms screen Salpingoeca rosetta with curated library human inhibitors. We identified 95 inhibitors disrupt S. proliferation. By exploring structure-activity relationships one inhibitor, sorafenib, p38 regulator heat oxidative stress . This finding indicates conserved between choanoflagellates, fungi. Moreover, this demonstrates existing can serve powerful tools examine ancestral modern development.

Language: Английский

A stress-responsive p38 signaling axis in choanoflagellates DOI Creative Commons
Florentine U. Rutaganira, Maxwell C. Coyle, Maria Nguyen

et al.

RSC Chemical Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Animal kinases regulate cellular responses to environmental stimuli, including cell differentiation, migration, survival, and response stress, but the ancestry of these functions is poorly understood. Choanoflagellates, closest living relatives animals, encode homologs diverse animal have emerged as model organisms for reconstructing origins. However, efforts identify key kinase regulators in choanoflagellates been constrained by limitations currently available genetic tools. Here, we report on a framework that combines small molecule-driven discovery with targeted genetics reveal function choanoflagellates. To study physiological roles choanoflagellate kinases, established two high-throughput platforms screen Salpingoeca rosetta curated library human inhibitors. We identified 95 inhibitors disrupt S. proliferation. By focusing one inhibitor, sorafenib, p38 regulator heat shock rosetta. This finding reveals conserved between choanoflagellates, fungi. Moreover, this demonstrates existing can serve powerful tools examine ancestral modern development.

Language: Английский

Citations

0
Evolutionary analysis of p38 stress-activated kinases in unicellular relatives of animals suggests an ancestral function in osmotic stress DOI Creative Commons
Victoria Shabardina, Pedro Romero Charria, Gonzalo Bercedo Saborido

et al.

Open Biology, Journal Year: 2023, Volume and Issue: 13(1)

Published: Jan. 1, 2023

p38 kinases are key elements of the cellular stress response in animals. They mediate cell to a multitude stimuli, from osmotic shock inflammation and oncogenes. However, it is unknown how such diversity function evolved this kinase subfamily. Here, we show that was already present common ancestor animals fungi. Later, animals, diversified into three JNK four kinases. Moreover, identified fifth paralog fishes amphibians. Our analysis shows each has specific amino acid substitutions around hinge point, region between N-terminal C-terminal protein domains. We showed can be used distinguish individual paralogs predict their specificity. Finally, hyperosmotic Capsaspora owczarzaki, close unicellular relative follows phosphorylation-dephosphorylation pattern typical At same time, Capsaspora's cells upregulate expression GPD1 resembling an yeasts. Overall, our results ancestral pathway originated root opisthokonts, most likely as cell's reaction salinity change environment. In became more complex incorporated stimuli downstream targets due sequence evolution docking substrate binding sites region. This study improves understanding opens new perspectives for research.

Language: Английский

Citations

4
Mitogen-activated protein kinase (MAPK) cascades—A yeast perspective DOI
Lee Bardwell, Jeremy Thorner

˜The œEnzymes, Journal Year: 2023, Volume and Issue: unknown, P. 137 - 170

Published: Jan. 1, 2023

Language: Английский

Citations

2
p38α and p38β regulate osmostress-induced apoptosis DOI

Nabil Ben Messaoud,

José M. López

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 108061 - 108061

Published: Dec. 1, 2024

Language: Английский

Citations

0
A stress-responsive p38 signaling axis in choanoflagellates DOI Creative Commons
Florentine U. Rutaganira, Maxwell C. Coyle,

Alex Scopton

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Aug. 27, 2022

Abstract Animal kinases regulate cellular responses to environmental stimuli, including cell differentiation, migration, survival, and response stress, but the ancestry of these functions is poorly understood. Choanoflagellates, closest living relatives animals, encode homologs diverse animal have emerged as model organisms for reconstructing origins. However, efforts study kinase signaling in choanoflagellates been constrained by limitations currently available genetic tools. Here we demonstrate that small molecule approaches provide a complementary scalable approach studying function choanoflagellates. To physiological roles choanoflagellate kinases, established two high-throughput platforms screen Salpingoeca rosetta with curated library human inhibitors. We identified 95 inhibitors disrupt S. proliferation. By exploring structure-activity relationships one inhibitor, sorafenib, p38 regulator heat oxidative stress . This finding indicates conserved between choanoflagellates, fungi. Moreover, this demonstrates existing can serve powerful tools examine ancestral modern development.

Language: Английский

Citations

2