The oncoprotein I-2PP2A/SET negatively regulates the MEK/ERK pathway and cell proliferation

  • Authors:
    • Chikako Fukukawa
    • Hiroshi Shima
    • Nobuhiro Tanuma
    • Tadashi Okada
    • Natsue Kato
    • Yoshifumi Adachi
    • Kunimi Kikuchi
  • View Affiliations

  • Published online on: March 1, 2005     https://doi.org/10.3892/ijo.26.3.751
  • Pages: 751-756
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Abstract

I-2PP2A/SET, the translocation breakpoint-encoded protein expressed in acute undifferentiated leukemia, was identified as an inhibitor of protein phosphatase 2A (PP2A). Induction of exogenous I-2PP2A/SET at a ratio of 1:1 to the endogenous protein resulted in suppression of cell proliferation. In contrast, siRNA-mediated depletion of I-2PP2A/SET resulted in enhanced cell proliferation. Depletion of I-2PP2A/SET was accompanied with a decrease in the number of cells in G1 and an increase in cells in S phase. To examine the mode of action by which I-2PP2A/SET suppresses cell proliferation, we determined the effect of over-expressed I-2PP2A/SET on ERK activation. I-2PP2A/SET suppressed activation of ERK following EGF stimulation but did not affect activation levels of stress kinases, JNK and p38. By contrast, knocking down I-2PP2A/SET by siRNA resulted in enhancement of ERK and MEK activations, suggesting that I-2PP2A/SET negatively regulates MEK/ERK. These data suggest that I-2PP2A/SET negatively regulates cell growth by inhibiting the G1/S transition and inhibiting the MEK/ERK pathway stimulated by external stimuli. These data demonstrate that I-2PP2A/SET potentially functions as a tumor suppressor.

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March 2005
Volume 26 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Copy and paste a formatted citation
APA
Fukukawa, C., Shima, H., Tanuma, N., Okada, T., Kato, N., Adachi, Y., & Kikuchi, K. (2005). The oncoprotein I-2PP2A/SET negatively regulates the MEK/ERK pathway and cell proliferation. International Journal of Oncology, 26, 751-756. https://doi.org/10.3892/ijo.26.3.751
MLA
Fukukawa, C., Shima, H., Tanuma, N., Okada, T., Kato, N., Adachi, Y., Kikuchi, K."The oncoprotein I-2PP2A/SET negatively regulates the MEK/ERK pathway and cell proliferation". International Journal of Oncology 26.3 (2005): 751-756.
Chicago
Fukukawa, C., Shima, H., Tanuma, N., Okada, T., Kato, N., Adachi, Y., Kikuchi, K."The oncoprotein I-2PP2A/SET negatively regulates the MEK/ERK pathway and cell proliferation". International Journal of Oncology 26, no. 3 (2005): 751-756. https://doi.org/10.3892/ijo.26.3.751