GRB2 is a BECN1 interacting protein that regulates autophagy

Cell Death Dis. 2024 Jan 5;15(1):14. doi: 10.1038/s41419-023-06387-7.

Abstract

GRB2 is an adaptor protein of HER2 (and several other tyrosine kinases), which we identified as a novel BECN1 (Beclin 1) interacting partner. GRB2 co-immunoprecipitated with BECN1 in several breast cancer cell lines and regulates autophagy through a mechanism involving the modulation of the class III PI3Kinase VPS34 activity. In ovo studies in a CAM (Chicken Chorioallantoic Membrane) model indicated that GRB2 knockdown, as well as overexpression of GRB2 loss-of-function mutants (Y52A and S86A-R88A) compromised tumor growth. These differences in tumor growth correlated with differential autophagy activity, indicating that autophagy effects might be related to the effects on tumorigenesis. Our data highlight a novel function of GRB2 as a BECN1 binding protein and a regulator of autophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Autophagy*
  • Beclin-1* / metabolism
  • Carcinogenesis
  • Cell Transformation, Neoplastic
  • GRB2 Adaptor Protein* / metabolism
  • Humans

Substances

  • Adaptor Proteins, Signal Transducing
  • Beclin-1
  • GRB2 protein, human
  • BECN1 protein, human
  • GRB2 Adaptor Protein