Journal
CELLULAR SIGNALLING
Volume 24, Issue 7, Pages 1369-1374Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2012.03.004
Keywords
Fer; ROS; ATM; p53; Colon carcinoma cells
Categories
Funding
- Israeli Ministry of Health - Chief Scientist Research Foundation
- Elias, Genevieve and Geogiana Atol Charitable Trust
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Fer is an intracellular tyrosine kinase which resides in both the cytoplasm and nucleus of mammalian cells. This kinase was also found in all malignant cell-lines analyzed and was shown to support cell-cycle progression in cancer cells. Herein we show that knock-down of Fer, both, impairs cell-cycle progression and imposes programmed cell death in colon carcinoma (CC) cells. The cell-cycle arrest and apoptotic death invoked by the depletion of Fer were found to depend on the activity of p53. Accordingly, down regulation of Fer led to the activation of the Ataxia Telangiectasia Mutated protein (ATM) and its down-stream effector-p53. Knock-down of Fer also increased the level of Reactive-Oxygen Species (ROS) in CC cells, and subjection of Fer depleted cells to ROS neutralizing scavengers significantly decreased the induced phosphorylation and activation of ATM and p53. Notably, over-expression of Fer opposed the Doxorubicin driven activation of ATM and p53, which can be mediated by ROS. Collectively, our findings imply that Fer sustains low ROS levels in CC cells, thereby restraining the activation of ATM and p53 in these cells. (c) 2012 Elsevier Inc. All rights reserved.
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