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Inhibition of tumor suppressor p73 by nerve growth factor receptor via chaperone-mediated autophagy

Daniel Nguyen1, Kun Yang1, Lucia Chiao1,2

  • 1Department of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112, USA.

Journal of Molecular Cell Biology
|April 15, 2020
PubMed

Insights

The tumor suppressor p73 is negatively regulated by nerve growth factor receptor (NGFR). NGFR promotes p73 degradation via chaperone-mediated autophagy, impacting cancer cell apoptosis.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cellular Signaling

Background:

  • The tumor suppressor p73, a p53 homolog, induces cell cycle arrest and apoptosis.
  • Understanding p73 regulation is crucial for cancer therapy.

Purpose of the Study:

  • To identify novel regulators of p73.
  • To elucidate the mechanism by which NGFR affects p73 function.

Main Methods:

  • Gene expression analysis
  • Protein-protein interaction studies
  • Cellular degradation assays
  • Chaperone-mediated autophagy pathway investigation

Main Results:

  • Nerve growth factor receptor (NGFR) was identified as a novel negative regulator of p73.
  • p73 activates NGFR transcription, creating a negative feedback loop.
  • NGFR binds to the p73 DNA-binding domain, inhibiting its transcriptional activity and p73-mediated apoptosis.
  • NGFR facilitates p73 degradation through the chaperone-mediated autophagy (CMA) pathway.

Conclusions:

  • NGFR inactivates p73 tumor suppressor activity.
  • NGFR promotes p73 degradation via CMA, revealing a new oncogenic mechanism.
  • Targeting the NGFR/p73/CMA axis may offer therapeutic strategies in cancer.
Keywords:
HSPA8Lamp2aNGFRchaperone-mediated autophagyp73

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