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Study of Protein-protein Interactions in Autophagy Research
14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

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A kinase-independent role for EGF receptor in autophagy initiation

Xiaojun Tan1, Narendra Thapa1, Yue Sun1

  • 1Program in Molecular and Cellular Pharmacology, University of Wisconsin-Madison School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.

Cell
|January 17, 2015
PubMed

Insights

Inactive epidermal growth factor receptor (EGFR) initiates autophagy through interaction with LAPTM4B and Sec5. This pathway regulates tumor cell metabolism and survival during stress.

Area of Science:

  • Cellular biology
  • Cancer research
  • Molecular oncology

Background:

  • Epidermal growth factor receptor (EGFR) is often upregulated in human cancers.
  • EGFR signaling inhibition can trigger autophagy in tumor cells.

Purpose of the Study:

  • To investigate the role of inactive EGFR in autophagy initiation.
  • To elucidate the molecular mechanisms linking inactive EGFR to autophagy.

Main Methods:

  • Co-immunoprecipitation assays to study protein interactions.
  • Western blotting to assess protein levels and autophagy markers.
  • Immunofluorescence microscopy to visualize protein localization.

Main Results:

  • Inactive EGFR interacts with the oncoprotein LAPTM4B, crucial for EGFR endosomal accumulation during serum starvation.
  • Inactive EGFR, LAPTM4B, and the Sec5 subcomplex are essential for both basal and starvation-induced autophagy.
  • LAPTM4B and Sec5 facilitate the association of EGFR with Rubicon, leading to Beclin 1 release and autophagy initiation.

Conclusions:

  • The oncoprotein LAPTM4B mediates the role of inactive EGFR in initiating autophagy.
  • This newly identified pathway involving inactive EGFR, LAPTM4B, and Sec5 regulates tumor cell metabolism and survival under metabolic stress.

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