GRB2 is a BECN1 interacting protein that regulates autophagy

被引：2

作者：

Montero-Vergara, Jetsy ^{[1
]}

Plachetta, Kira ^{[1
]}

Kinch, Lisa ^{[2
]}

Bernhardt, Stephan ^{[3
]}

Kashyap, Kriti ^{[4
]}

Levine, Beth ^{[2
]}

Thukral, Lipi ^{[4
,5
]}

Vetter, Martina ^{[6
]}

Thomssen, Christoph ^{[6
]}

Wiemann, Stefan ^{[3
]}

Pena-Llopis, Samuel ^{[7
,8
,9
]}

Jendrossek, Verena ^{[1
]}

Vega-Rubin-de-Celis, Silvia ^{[1
]}

机构：

[1] Univ Hosp Essen, Inst Cell Biol Canc Res, Virchowstr 173, D-45147 Essen, Germany

[2] Univ Texas Southwestern Med Ctr Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 USA

[3] German Canc Res Ctr, Div Mol Genome Anal, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

[4] CSIR Inst Genom & Integrat Biol, Mathura Rd, New Delhi 110025, Delhi, India

[5] Acad Sci & Innovat Res AcSIR, Ghaziabad 201002, India

[6] Martin Luther Univ Halle Wittenberg, Dept Gynaecol, Ernst Grube Str 40, D-06120 Halle, Saale, Germany

[7] Univ Hosp Essen, Translat Genom, Dept Ophthalmol, Essen, Germany

[8] German Canc Consortium DKTK, Heidelberg, Germany

[9] German Canc Res Ctr, Heidelberg, Germany

来源：

CELL DEATH & DISEASE | 2024年 / 15卷 / 01期

基金：

欧盟地平线“2020”;

关键词：

GROWTH-FACTOR RECEPTOR; TYROSINE PHOSPHORYLATION; SH2;

D O I：

10.1038/s41419-023-06387-7

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：11

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