Casein kinase I down-regulates phospho-Akt via PTEN, following genotoxic stress-induced apoptosis in hematopoietic cells
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- 作者：Atsuo Okamura ; Nobuko Iwata ; Akira Tamekane ; Kimikazu Yakushijin ; Shinichiro Nishikawa ; Miyuki Hamaguchi ; Chie Fukui ; Katsuya Yamamoto and Toshimitsu Matsui
- 关键词：Casein kinase I
; //www.sciencedirect.com/scidirimg/entities/25b.gif"" alt=""var epsilon"" border=0> ; Akt ; PTEN ; Cell survival ; Leukomogenesis
- 刊名：Life Sciences
- 出版年：2006
- 出版时间：28 February 2006
- 年：2006
- 卷：78
- 期：14
- 页码：1624-1629
- 全文大小：147 K
文摘
Here, we show a functional role of casein kinase I (CKI) in hematopoietic cell survival through the modification of phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Introduction of wild-type (WT)-CKI into interleukin-3 (IL-3)-dependent 32D cells increased the sensitivity to genotoxic stresses, such as γ-irradiation, etoposide, and IL-3 deprivation, whereas kinase-negative (KN)-CKI suppressed it. Contrary to KN-CKI, WT-CKI 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 CKI expression induced by all-trans retinoic acid and by the addition of a specific inhibitor for CKI in HL-60 cells. CKI seems to activate PTEN by physical interaction. These results suggest that the CKI-induced down-regulation of PI3K/Akt signaling through PTEN lead to amplified sensitivity to apoptosis. Thus, the suppression of CKI in many human leukemia cell lines may play a role in the cell immortalization.