TY - JOUR AU - Montero-Vergara, Jetsy AU - Plachetta, Kira AU - Kinch, Lisa AU - Bernhardt, Stephan AU - Kashyap, Kriti AU - Levine, Beth AU - Thukral, Lipi AU - Vetter, Martina AU - Thomssen, Christoph AU - Wiemann, Stefan AU - Peña-Llopis, Samuel AU - Jendrossek, Verena AU - Vega-Rubin-de-Celis, Silvia TI - GRB2 is a BECN1 interacting protein that regulates autophagy. JO - Cell death & disease VL - 15 IS - 1 SN - 2041-4889 CY - London [u.a.] PB - Nature Publishing Group M1 - DKFZ-2024-00053 SP - 14 PY - 2024 AB - 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. LB - PUB:(DE-HGF)16 C6 - pmid:38182563 C2 - pmc:PMC10770341 DO - DOI:10.1038/s41419-023-06387-7 UR - https://inrepo02.dkfz.de/record/286713 ER -