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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Authors | Chikako Fukukawa, Hiroshi Shima, Nobuhiro Tanuma, Tadashi Okada, Natsue Kato, Yoshifumi Adachi, Kunimi Kikuchi |
Journal | International journal of oncology
(Int J Oncol)
Vol. 26
Issue 3
Pg. 751-6
(Mar 2005)
ISSN: 1019-6439 [Print] Greece |
PMID | 15703833
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chromosomal Proteins, Non-Histone
- DNA-Binding Proteins
- Histone Chaperones
- SET protein, human
- Transcription Factors
- Extracellular Signal-Regulated MAP Kinases
- MAP Kinase Kinase Kinases
- Phosphoprotein Phosphatases
- Protein Phosphatase 2
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Topics |
- Cell Cycle
- Cell Proliferation
- Chromosomal Proteins, Non-Histone
(genetics, pharmacology)
- DNA-Binding Proteins
- Extracellular Signal-Regulated MAP Kinases
(pharmacology)
- Gene Expression Profiling
- HeLa Cells
- Histone Chaperones
- Humans
- MAP Kinase Kinase Kinases
(pharmacology)
- Phosphoprotein Phosphatases
(genetics, pharmacology)
- Protein Phosphatase 2
- Transcription Factors
(genetics, pharmacology)
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