Osmotic stress regulates the stability of cyclin D1 in a p38SAPK2-dependent manner.
J Biol Chem
; 275(45): 35091-7, 2000 Nov 10.
Article
in En
| MEDLINE
| ID: mdl-10952989
ABSTRACT
We report here that different cell stresses regulate the stability of cyclin D1 protein. Exposition of Granta 519 cells to osmotic shock, oxidative stress, and arsenite induced the post-transcriptional down-regulation of cyclin D1. In the case of osmotic shock, this effect was completely reversed by the addition of p38(SAPK2)-specific inhibitors (SB203580 or SB220025), indicating that this effect is dependent on p38(SAPK2) activity. Moreover, the use of proteasome inhibitors prevented this down-regulation. Thus, osmotic shock induces proteasomal degradation of cyclin D1 protein by a p38(SAPK2)-dependent pathway. The effect of p38(SAPK2) on cyclin D1 stability might be mediated by direct phosphorylation at specific sites. We found that p38(SAPK2) phosphorylates cyclin D1 in vitro at Thr(286) and that this phosphorylation triggers the ubiquitination of cyclin D1. These results link for the first time a stress-induced MAP kinase pathway to cyclin D1 protein stability, and they will help to understand the molecular mechanisms by which stress transduction pathways regulate the cell cycle machinery and take control over cell proliferation.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osmosis
/
Cyclin D1
/
Mitogen-Activated Protein Kinases
Language:
En
Journal:
J Biol Chem
Year:
2000
Document type:
Article
Affiliation country:
Spain