RIG1 suppresses Ras activation and induces cellular apoptosis at the Golgi apparatus

Retinoid-inducible gene 1 encodes RIG1 is a growth regulator, which inhibits the pathways of the RAS/mitogen-activated protein kinases by suppressing the activation of RAS. Confocal microscopic analysis demonstrated that RIG1 is localized in the endoplasmic reticulum (ER) and Golgi apparatus in HtTA...

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Bibliographic Details
Published in:Cellular signalling 2007-05, Vol.19 (5), p.989-999
Main Authors: Tsai, Fu-Ming, Shyu, Rong-Yaun, Jiang, Shun-Yuan
Format: Article
Language:English
Subjects:
Apoptosis
Caspase
Caspase Inhibitors
Caspases - metabolism
Endoplasmic Reticulum - metabolism
Epidermal Growth Factor - metabolism
Golgi apparatus
Golgi Apparatus - metabolism
HeLa Cells
Humans
Proto-Oncogene Proteins p21(ras) - antagonists & inhibitors
Proto-Oncogene Proteins p21(ras) - metabolism
RARRES3
RAS
Receptors, Retinoic Acid - metabolism
RIG1
TIG3
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Summary:Retinoid-inducible gene 1 encodes RIG1 is a growth regulator, which inhibits the pathways of the RAS/mitogen-activated protein kinases by suppressing the activation of RAS. Confocal microscopic analysis demonstrated that RIG1 is localized in the endoplasmic reticulum (ER) and Golgi apparatus in HtTA cervical cancer cells. Carboxyterminal-deleted RIG1 targeted to the Golgi or ER was constructed and validated. The activation of HRAS was inhibited by 25.1% or 81.4% in cells cotransfected with wild-type or Golgi-targeted RIG1, respectively. Expression of wild-type or Golgi-targeted RIG1 for 24 h induced cellular apoptosis in HtTA cells, as assessed by MTT assay, the release of lactate dehydrogenase, and chromatin condensation. In contrast, ER-targeted RIG1 and carboxyterminal-deleted RIG1 (RIG1ΔC) exhibited no activity. Caspase-2, -3, and -9 were activated following the expression of wild-type and Golgi-targeted RIG1. Although the caspase-3 inhibitor Z-DEVD-FMK partially or completely reversed the cell death induced by wild-type or Golgi-targeted RIG1, it did not prevent the anti-RAS effect of RIG1. In conclusion, the proapoptotic and anti-RAS activities of RIG1 are primarily associated with the Golgi localization of the protein. The proapoptotic activities of RIG1 are mediated through the activation of caspase-2 and -3 and are independent of its effect on RAS.
ISSN:0898-6568
1873-3913
DOI:10.1016/j.cellsig.2006.11.005