Casein kinase Iepsilon down-regulates phospho-Akt via PTEN, following genotoxic stress-induced apoptosis in hematopoietic cells

Here, we show a functional role of casein kinase I (CKI) epsilon in hematopoietic cell survival through the modification of phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Introduction of wild-type (WT)-CKIepsilon into interleukin-3 (IL-3)-dependent 32D cells increased the sensitivity to genotox...

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Bibliographic Details
Published in:Life sciences (1973) 2006-02, Vol.78 (14), p.1624-1629
Main Authors: Okamura, Atsuo, Iwata, Nobuko, Tamekane, Akira, Yakushijin, Kimikazu, Nishikawa, Shinichiro, Hamaguchi, Miyuki, Fukui, Chie, Yamamoto, Katsuya, Matsui, Toshimitsu
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Casein Kinase Iepsilon - metabolism
Cell Line, Tumor
DNA Damage
Down-Regulation
Hematopoietic Stem Cells - enzymology
Hematopoietic Stem Cells - physiology
Humans
Mice
Phosphatidylinositol 3-Kinases - metabolism
Phosphorylation
Proto-Oncogene Proteins c-akt - metabolism
PTEN Phosphohydrolase - metabolism
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Summary:Here, we show a functional role of casein kinase I (CKI) epsilon in hematopoietic cell survival through the modification of phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Introduction of wild-type (WT)-CKIepsilon into interleukin-3 (IL-3)-dependent 32D cells increased the sensitivity to genotoxic stresses, such as gamma-irradiation, etoposide, and IL-3 deprivation, whereas kinase-negative (KN)-CKIepsilon suppressed it. Contrary to KN-CKIepsilon, WT-CKIepsilon attenuated the IL-3-induced activation of Akt with the increase of PTEN activity. Similarly, the increase of Akt activation, as well as PTEN inactivation, was accompanied both by a decrease of CKIepsilon expression induced by all-trans retinoic acid and by the addition of a specific inhibitor for CKIepsilon in HL-60 cells. CKIepsilon seems to activate PTEN by physical interaction. These results suggest that the CKIepsilon-induced down-regulation of PI3K/Akt signaling through PTEN lead to amplified sensitivity to apoptosis. Thus, the suppression of CKIepsilon in many human leukemia cell lines may play a role in the cell immortalization.
ISSN:0024-3205