Modulating p38 MAPK signaling by proteostasis mechanisms supports tissue integrity during growth and aging
© 2023. The Author(s)..
The conserved p38 MAPK family is activated by phosphorylation during stress responses and inactivated by phosphatases. C. elegans PMK-1 p38 MAPK initiates innate immune responses and blocks development when hyperactivated. Here we show that PMK-1 signaling is enhanced during early aging by modulating the stoichiometry of non-phospho-PMK-1 to promote tissue integrity and longevity. Loss of pmk-1 function accelerates progressive declines in neuronal integrity and lysosome function compromising longevity which has both cell autonomous and cell non-autonomous contributions. CED-3 caspase cleavage limits phosphorylated PMK-1. Enhancing p38 signaling with caspase cleavage-resistant PMK-1 protects lysosomal and neuronal integrity extending a youthful phase. PMK-1 works through a complex transcriptional program to regulate lysosome formation. During early aging, the absolute phospho-p38 amount is maintained but the reservoir of non-phospho-p38 diminishes to enhance signaling without hyperactivation. Our findings show that modulating the stoichiometry of non-phospho-p38 dynamically supports tissue-homeostasis during aging without hyper-activation of stress response.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
|---|---|
| Enthalten in: |
Nature communications - 14(2023), 1 vom: 28. Juli, Seite 4543 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Yuan, Wang [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 31.07.2023 Date Revised 02.08.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41467-023-40317-7 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM360073174 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM360073174 | ||
| 003 | DE-627 | ||
| 005 | 20231226082232.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-023-40317-7 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1200.xml |
| 035 | |a (DE-627)NLM360073174 | ||
| 035 | |a (NLM)37507441 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Yuan, Wang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Modulating p38 MAPK signaling by proteostasis mechanisms supports tissue integrity during growth and aging |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 31.07.2023 | ||
| 500 | |a Date Revised 02.08.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a The conserved p38 MAPK family is activated by phosphorylation during stress responses and inactivated by phosphatases. C. elegans PMK-1 p38 MAPK initiates innate immune responses and blocks development when hyperactivated. Here we show that PMK-1 signaling is enhanced during early aging by modulating the stoichiometry of non-phospho-PMK-1 to promote tissue integrity and longevity. Loss of pmk-1 function accelerates progressive declines in neuronal integrity and lysosome function compromising longevity which has both cell autonomous and cell non-autonomous contributions. CED-3 caspase cleavage limits phosphorylated PMK-1. Enhancing p38 signaling with caspase cleavage-resistant PMK-1 protects lysosomal and neuronal integrity extending a youthful phase. PMK-1 works through a complex transcriptional program to regulate lysosome formation. During early aging, the absolute phospho-p38 amount is maintained but the reservoir of non-phospho-p38 diminishes to enhance signaling without hyperactivation. Our findings show that modulating the stoichiometry of non-phospho-p38 dynamically supports tissue-homeostasis during aging without hyper-activation of stress response | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Mitogen-Activated Protein Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.24 |2 NLM | |
| 650 | 7 | |a Caenorhabditis elegans Proteins |2 NLM | |
| 650 | 7 | |a p38 Mitogen-Activated Protein Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.24 |2 NLM | |
| 650 | 7 | |a Caspases |2 NLM | |
| 650 | 7 | |a EC 3.4.22.- |2 NLM | |
| 700 | 1 | |a Weaver, Yi M |e verfasserin |4 aut | |
| 700 | 1 | |a Earnest, Svetlana |e verfasserin |4 aut | |
| 700 | 1 | |a Taylor, Clinton A |c 4th |e verfasserin |4 aut | |
| 700 | 1 | |a Cobb, Melanie H |e verfasserin |4 aut | |
| 700 | 1 | |a Weaver, Benjamin P |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 14(2023), 1 vom: 28. Juli, Seite 4543 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
| 773 | 1 | 8 | |g volume:14 |g year:2023 |g number:1 |g day:28 |g month:07 |g pages:4543 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-023-40317-7 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 14 |j 2023 |e 1 |b 28 |c 07 |h 4543 | ||