Down-regulation of Fer induces ROS levels accompanied by ATM and p53 activation in colon carcinoma cells

Adar Makovski, Etai Yaffe, Sally Shpungin, Uri Nir

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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.

Original languageEnglish
Pages (from-to)1369-1374
Number of pages6
JournalCellular Signalling
Issue number7
StatePublished - Jul 2012

Bibliographical note

Funding Information:
This work was supported by a grant from the Israeli Ministry of Health – Chief Scientist Research Foundation and by the Elias, Genevieve and Geogiana Atol Charitable Trust .


  • ATM
  • Colon carcinoma cells
  • Fer
  • P53
  • ROS


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