GADD34 inhibits mammalian target of rapamycin signaling via tuberous sclerosis complex and controls cell survival under bioenergetic stress

  • Authors:
    • Ryosuke Watanabe
    • Yukihiro Tambe
    • Hirokazu Inoue
    • Takahiro Isono
    • Masataka Haneda
    • Ken-ichi Isobe
    • Toshiyuki Kobayashi
    • Okio Hino
    • Hidetoshi Okabe
    • Tokuhiro Chano
  • View Affiliations

  • Published online on: March 1, 2007     https://doi.org/10.3892/ijmm.19.3.475
  • Pages: 475-483
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Abstract

Cells regulate the rate of protein synthesis during conditions of cell stress to adapt to environmental changes. However, the molecular interactions between signaling pathways controlling translation and the cellular response to stress remain to be elucidated. Here, we show that the expression of growth arrest and DNA damage protein 34 (GADD34) is induced by energy depletion and that the expression of this protein protects cells from apoptotic cell death. During conditions of cell stress, GADD34 forms a stable complex with tuberous sclerosis complex (TSC) 1/2, causes TSC2 dephosphorylation, and inhibits signaling by mammalian target of the rapamycin (mTOR). These findings demonstrate that crosstalk between GADD34 and the mTOR signaling pathways contributes to the response of the protein synthetic machinery to environmental stress. GADD34 may find clinical potential as a target drug for the treatment of mTOR-associated diseases.

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March 2007
Volume 19 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Watanabe, R., Tambe, Y., Inoue, H., Isono, T., Haneda, M., Isobe, K. ... Chano, T. (2007). GADD34 inhibits mammalian target of rapamycin signaling via tuberous sclerosis complex and controls cell survival under bioenergetic stress. International Journal of Molecular Medicine, 19, 475-483. https://doi.org/10.3892/ijmm.19.3.475
MLA
Watanabe, R., Tambe, Y., Inoue, H., Isono, T., Haneda, M., Isobe, K., Kobayashi, T., Hino, O., Okabe, H., Chano, T."GADD34 inhibits mammalian target of rapamycin signaling via tuberous sclerosis complex and controls cell survival under bioenergetic stress". International Journal of Molecular Medicine 19.3 (2007): 475-483.
Chicago
Watanabe, R., Tambe, Y., Inoue, H., Isono, T., Haneda, M., Isobe, K., Kobayashi, T., Hino, O., Okabe, H., Chano, T."GADD34 inhibits mammalian target of rapamycin signaling via tuberous sclerosis complex and controls cell survival under bioenergetic stress". International Journal of Molecular Medicine 19, no. 3 (2007): 475-483. https://doi.org/10.3892/ijmm.19.3.475