Abstract
Cells form stress granules (SGs), in response to unfavorable environments, to avoid apoptosis, but it is unclear whether and how SG formation and cellular apoptosis are coordinately regulated. In this study we detected the small GTPase, Ras homolog gene family member A (RhoA), and its downstream kinase, Rho-associated, coiled-coil containing protein kinase 1 (ROCK1), in SG, and found that their stress-induced activities were important for SG formation and subsequent global translational repression. Importantly, only activated RhoA and ROCK1 were sequestered into SG. Sequestration of activated ROCK1 into SG prevented ROCK1 from interacting with JNK-interacting protein 3 (JIP-3) and its activation of c-Jun N-terminal kinase (JNK), a pathway triggering apoptosis, thereby protecting cells from apoptosis. This study identifies a specific signaling pathway, mediated by RhoA and ROCK1, which determines cell fate by promoting SG formation or initiating apoptosis during stress.
Original language | English (US) |
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Pages (from-to) | 668-675 |
Number of pages | 8 |
Journal | Cellular Signalling |
Volume | 22 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2010 |
Externally published | Yes |
Keywords
- Apoptosis
- JIP-3
- JNK
- P19
- ROCK1
- RhoA
- Stress granules
ASJC Scopus subject areas
- Cell Biology