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.
Jetsy Montero-Vergara  1 ,  Kira Plachetta  1 ,  Lisa Kinch  2 ,  Stephan Bernhardt  3 ,  Kriti Kashyap  4 ,  Beth Levine  2 ,  Lipi Thukral  4  5 ,  Martina Vetter  6 ,  Christoph Thomssen  6 ,  Stefan Wiemann  3 ,  Samuel Peña-Llopis  7  8 ,  Verena Jendrossek  1 ,  Silvia Vega-Rubin-de-Celis  9
Affiliations
  • 1. Institute of Cell Biology (Cancer Research), University Hospital Essen, Virchowstrasse 173, D-45122, Essen, Germany.
  • 2. University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390, USA.
  • 3. Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120, Heidelberg, Germany.
  • 4. CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi, Delhi, 110025, India.
  • 5. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
  • 6. Department of Gynaecology, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, D-06120, Halle (Saale), Germany.
  • 7. Translational Genomics. Department of Ophthalmology, University Hospital Essen, Essen, Germany.
  • 8. German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 9. Institute of Cell Biology (Cancer Research), University Hospital Essen, Virchowstrasse 173, D-45122, Essen, Germany. [email protected].
PMID: 38182563 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.

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