Oxidative stress-induced ubiquitination of RCAN1 mediated by SCFβ-TrCP ubiquitin ligase

  • Authors:
    • Sachie Asada
    • Akemi Ikeda
    • Rina Nagao
    • Hiroshi Hama
    • Tatsuhiko Sudo
    • Akiyoshi Fukamizu
    • Yoshitoshi Kasuya
    • Tsutomu Kishi
  • View Affiliations

  • Published online on: July 1, 2008     https://doi.org/10.3892/ijmm.22.1.95
  • Pages: 95-104
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Abstract

A change in the protein level of RCAN1 (DSCR1/MCIP/Adapt78/CSP1) has been implicated in oxidative stress-induced cell death in neurons and in the pathogenesis of Alzheimer's disease. The pathogenic processes in neurodegenerative diseases are closely related to oxidative stress and the ubiquitin proteasome system (UPS). Therefore, we investigated whether oxidative stress induces a change in the protein level of RCAN1 through the UPS. H2O2 induced ubiquitination of RCAN1 at the same concentrations as those causing a decrease in RCAN1 in HEK293T cells. β-TrCP, the F-box protein component of SCF ubiquitin ligase, interacted with RCAN1 in response to H2O2 stimulation. Although FBW4, another F-box protein, interacted with RCAN1, its interaction was independent of H2O2 stimulation. In vitro ubiquitination assay showed that SCFβ-TrCP but not SCFFBW4 increased ubiquitination of RCAN1, dependent on H2O2 stimulation. In addition, knockdown of β-TrCP by siRNA abolished the H2O2-induced decrease in RCAN1 in HEK293T cells. We further examined whether RCAN1 undergoes ubiquitination by H2O2 in primary neurons, similarly to that in HEK293T cells. An H2O2-induced decrease in RCAN1 was exhibited also in hippocampal and cortical neurons. Ubiquitination of RCAN1 was induced by 500 μM H2O2, the concentration at which H2O2 induced a decrease in RCAN1 in primary neurons. These results suggest that H2O2 induces SCFβ-TrCP-mediated ubiquitination of RCAN1, leading to a decrease in the protein level of RCAN1.

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July 2008
Volume 22 Issue 1

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

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Spandidos Publications style
Asada S, Ikeda A, Nagao R, Hama H, Sudo T, Fukamizu A, Kasuya Y and Kishi T: Oxidative stress-induced ubiquitination of RCAN1 mediated by SCFβ-TrCP ubiquitin ligase. Int J Mol Med 22: 95-104, 2008
APA
Asada, S., Ikeda, A., Nagao, R., Hama, H., Sudo, T., Fukamizu, A. ... Kishi, T. (2008). Oxidative stress-induced ubiquitination of RCAN1 mediated by SCFβ-TrCP ubiquitin ligase. International Journal of Molecular Medicine, 22, 95-104. https://doi.org/10.3892/ijmm.22.1.95
MLA
Asada, S., Ikeda, A., Nagao, R., Hama, H., Sudo, T., Fukamizu, A., Kasuya, Y., Kishi, T."Oxidative stress-induced ubiquitination of RCAN1 mediated by SCFβ-TrCP ubiquitin ligase". International Journal of Molecular Medicine 22.1 (2008): 95-104.
Chicago
Asada, S., Ikeda, A., Nagao, R., Hama, H., Sudo, T., Fukamizu, A., Kasuya, Y., Kishi, T."Oxidative stress-induced ubiquitination of RCAN1 mediated by SCFβ-TrCP ubiquitin ligase". International Journal of Molecular Medicine 22, no. 1 (2008): 95-104. https://doi.org/10.3892/ijmm.22.1.95