Journal Article

DKFZ-2024-00053

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png GRB2 is a BECN1 interacting protein that regulates autophagy.

Montero-Vergara, J. ; Plachetta, K. ; Kinch, L. ; Bernhardt, S.DKFZ* ; Kashyap, K. ; Levine, B. ; Thukral, L. ; Vetter, M. ; Thomssen, C. ; Wiemann, S.DKFZ* ; Peña-Llopis, S.DKFZ* ; Jendrossek, V. ; Vega-Rubin-de-Celis, S.

2024
Nature Publishing Group London [u.a.]

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Please use a persistent id in citations: 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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Contributing Institute(s):

1. B050 Molekulare Genomanalyse (B050)
2. DKTK Koordinierungsstelle Essen/Düsseldorf (ED01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2024

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