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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. © 2024. The Author(s).

Citation

Jetsy Montero-Vergara, Kira Plachetta, Lisa Kinch, Stephan Bernhardt, Kriti Kashyap, Beth Levine, Lipi Thukral, Martina Vetter, Christoph Thomssen, Stefan Wiemann, Samuel Peña-Llopis, Verena Jendrossek, Silvia Vega-Rubin-de-Celis. GRB2 is a BECN1 interacting protein that regulates autophagy. Cell death & disease. 2024 Jan 05;15(1):14

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PMID: 38182563

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