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GRB2 is a BECN1 interacting protein that regulates autophagy.

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.

SUBMITTER: Montero-Vergara J

PROVIDER: S-EPMC10770341 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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GRB2 is a BECN1 interacting protein that regulates autophagy.

Montero-Vergara Jetsy J Plachetta Kira K Kinch Lisa L Bernhardt Stephan S Kashyap Kriti K Levine Beth B Thukral Lipi L Vetter Martina M Thomssen Christoph C Wiemann Stefan S Peña-Llopis Samuel S Jendrossek Verena V Vega-Rubin-de-Celis Silvia S

Cell death & disease 20240105 1

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-R8 ...[more]

PMID: 38182563

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