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Study of Protein-protein Interactions in Autophagy Research
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Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

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

Luigi Moretti1, Albert Attia, Kwang Woon Kim

  • 1Department of Radiation Oncology, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-5671, USA.

Autophagy
|January 6, 2007
PubMed

Insights

Inhibiting apoptosis via Bax/Bak knockout paradoxically increased radiosensitivity, suggesting autophagy regulates cell death in response to radiation. This highlights autophagy

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Radiation oncology

Background:

  • Bax and Bak proteins are key mediators of apoptosis (programmed cell death).
  • The mTOR pathway regulates cell proliferation, growth, and survival.
  • Apoptosis is a limited cell death pathway in irradiated solid tumors, while autophagy can be induced.

Purpose of the Study:

  • To investigate alternative cell death pathways induced by radiation in Bax/Bak double knockout (DKO) cells.
  • To compare the radiosensitivity of Bax/Bak DKO cells versus wild-type cells.
  • To explore the role of autophagy in regulating cellular response to radiation.

Main Methods:

  • Irradiation of Bax/Bak DKO MEF cells and wild-type cells.
  • Assessment of cell survival and radiosensitivity.
  • Analysis of pro-autophagic proteins (ATG5-ATG12, Beclin-1) expression.

Main Results:

  • Bax/Bak DKO cells exhibited increased radiosensitivity compared to wild-type cells.
  • Irradiated cells showed elevated levels of pro-autophagic proteins ATG5-ATG12 and Beclin-1.
  • Radiation exposure upregulated autophagic programmed cell death in cells lacking Bax/Bak-mediated apoptosis.

Conclusions:

  • Inhibition of apoptosis does not necessarily equate to increased radioresistance; autophagy appears to be a critical regulator of radiosensitivity.
  • Bax/Bak may function as a negative regulator of autophagy, potentially through interaction with phosphatases like PTEN.
  • Targeting Bax/Bak and autophagy pathways presents potential strategies for enhancing cancer radiotherapy.

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