RhoA/ROCK1 signaling regulates stress granule formation and apoptosis.
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.
Tsai
Nien-Pei
NP
Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church St. SE, Minneapolis, MN 55455, USA.
Wei
Li-Na
LN
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D003594:Cytoplasmic Granules / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D054460:rho-Associated Kinases / Q000032:analysis / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000032:analysis / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C403619:Mapk8ip3 protein, mouse; D009419:Nerve Tissue Proteins; C515854:Rock1 protein, mouse; D054460:rho-Associated Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020742:rhoA GTP-Binding Protein