Crosstalk between Bak/bax and mTOR signaling regulates radiation-induced autophagy

Luigi Moretti, Albert Attia, Kwang Woon Kim, Bo Lu

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Bax and Bak, act as a gateway for caspase-mediated cell death. mTOR, an Akt downstream effector, plays a critical role in cell proliferation, growth and survival. The inhibition of mTOR induces autophagy, whereas apoptosis is a minor cell death mechanism in irradiated solid tumors. We explored possible alternative pathways for cell death induced by radiation in Bax/Bak -/- double knockout (DKO) MEF cells and wild-type cells, and we compared the cell survival: the Bax/Bak-/- cells were more radiosensitive than the wild-type cells. The irradiated cells displayed an increase in the pro-autophagic proteins ATG5-ATG12 and Beclin-1. These results are surprising in the fact that the inhibition of apoptosis resulted in increasing radiosensitivity; indicating that perhaps autophagy is the cornerstone in the cell radiation sensitivity regulation. Furthermore, irradiation upregulates autophagic programmed cell death in cells that are unable to undergo Bax/Bak-mediated apoptosis. We hypothesize the presence of a phosphatase-possibly PTEN, an Akt/mTOR negative regulator that can be inhibited by Bax/Bak. This fits with our hypothesis of Bax/Bak as a downregulator of autophagy. We are currently conducting experiments to explore the relationship between apoptosis and autophagy. Future directions in research include strategies targeting Bax/Bak in cancer xenografts and exploring novel radiosensitizers targeting autophagy pathways.

Original languageEnglish (US)
Pages (from-to)142-144
Number of pages3
JournalAutophagy
Volume3
Issue number2
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

Keywords

  • Apoptosis
  • Autophagy
  • Bak
  • Bax
  • Cancer cell death
  • mTOR
  • Radiation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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