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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Akt signaling: a damaging interaction makes good

Alex Toker1

  • 1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. atoker@bidmc.harvard.edu

Trends in Biochemical Sciences
|July 1, 2008
PubMed

Insights

DNA-dependent protein kinase phosphorylates Akt at Ser473, a crucial step for cellular survival. This novel mechanism activates survival pathways in response to DNA damage in cells and mice.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • DNA Damage Response

Background:

  • Phosphorylation of Akt at Ser473 is vital for activating cellular survival pathways.
  • The precise mechanism of Akt Ser473 phosphorylation during DNA damage response is not fully understood.

Purpose of the Study:

  • To elucidate a novel mechanism for Akt activation in response to DNA-damaging insults.
  • To investigate the role of DNA-dependent protein kinase in Akt phosphorylation at Ser473.

Main Methods:

  • Experiments were conducted on cells and mice exposed to DNA-damaging agents.
  • Investigated the mediation of Akt Ser473 phosphorylation by DNA-dependent protein kinase at DNA double-strand break sites.

Main Results:

  • Identified DNA-dependent protein kinase as the mediator of Akt Ser473 phosphorylation at sites of DNA double-strand breaks.
  • Demonstrated that this phosphorylation event initiates a transcriptional program promoting cell survival.

Conclusions:

  • A novel pathway for Akt activation involving DNA-dependent protein kinase has been uncovered.
  • This mechanism is critical for cellular survival following DNA damage, highlighting a new therapeutic target.

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