ArticleMolecular biology of the cell2007
Endocytic down-regulation of ErbB2 is stimulated by cleavage of its C-terminus.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- Innately Fluorescent Tetravalent Cytotoxic Conjugate TetraFJournal of medicinal chemistry · 2025Article
- Irreversible tyrosine kinase inhibitors induce the endocytosis and downregulation of ErbB2.Biochemistry and biophysics reports · 2023Article
- EGFR trafficking: effect of dimerization, dynamics, and mutation.Frontiers in oncology · 2023Review
- Expanding the Disorder-Function Paradigm in the C-Terminal Tails of Erbbs.Biomolecules · 2021Review
- Impact of Endocytosis Mechanisms for the Receptors Targeted by the Currently Approved Antibody-Drug Conjugates (ADCs)-A Necessity for Future ADC Research and Development.Pharmaceuticals (Basel, Switzerland) · 2021Review
- The deubiquitylase USP2 maintains ErbB2 abundance via counteracting endocytic degradation and represents a therapeutic target in ErbB2-positive breast cancer.Cell death and differentiation · 2020Article
- Proteasome 26S Subunit, non-ATPase 3 (PSMD3) Regulates Breast Cancer by Stabilizing HER2 from Degradation.Cancers · 2019Article
- MEK inhibitors induce Akt activation and drug resistance by suppressing negative feedback ERK-mediated HER2 phosphorylation at Thr701.Molecular oncology · 2017Article
- Article
- Identification of an HSP90 modulated multi-step process for ERBB2 degradation in breast cancer cells.Oncotarget · 2016Article
- A combination of two antibodies recognizing non-overlapping epitopes of HER2 induces kinase activity-dependent internalization of HER2.Journal of cellular and molecular medicine · 2016Article
- Septin oligomerization regulates persistent expression of ErbB2/HER2 in gastric cancer cells.The Biochemical journal · 2016Article
- Regulation of ErbB2 localization and function in breast cancer cells by ERM proteins.Oncotarget · 2016Article
- Cellular Pathways in Response to Ionizing Radiation and Their Targetability for Tumor Radiosensitization.International journal of molecular sciences · 2016Review
- Septins: Regulators of Protein Stability.Frontiers in cell and developmental biology · 2016Review
- A kinase inhibitor screen reveals protein kinase C-dependent endocytic recycling of ErbB2 in breast cancer cells.The Journal of biological chemistry · 2014Article
- Role of Erbin in ErbB2-dependent breast tumor growth.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- The Mysterious Ways of ErbB2/HER2 Trafficking.Membranes · 2014Review
- The NF2 tumor suppressor regulates microtubule-based vesicle trafficking via a novel Rac, MLK and p38(SAPK) pathway.Oncogene · 2013Article
- Chronic morphine treatment attenuates cell growth of human BT474 breast cancer cells by rearrangement of the ErbB signalling network.PloS one · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High ErbB2 levels are associated with cancer, and impaired endocytosis of ErbB2 could contribute to its overexpression. Therefore, knowledge about the mechanisms underlying endocytic down-regulation of ErbB2 is warranted. The C-terminus of ErbB2 can be cleaved after various stimuli, and after inhibition of HSP90 with geldanamycin this cleavage is accompanied by proteasome-dependent endocytosis of ErbB2. However, it is unknown whether C-terminal cleavage is linked to endocytosis. To study ErbB2 cleavage and endocytic trafficking, we fused yellow fluorescent protein (YFP) and cyan fluorescent protein (CFP) to the N- and C-terminus of ErbB2, respectively (YFP-ErbB2-CFP). After geldanamycin stimulation YFP-ErbB2-CFP became cleaved in nonapoptotic cells in a proteasome-dependent manner, and a markedly larger relative amount of cleaved YFP-ErbB2-CFP was observed in early endosomes than in the plasma membrane. Furthermore, cleavage took place at the plasma membrane, and cleaved ErbB2 was internalized and degraded far more efficiently than full-length ErbB2. Concordantly, a C-terminally truncated ErbB2 was also readily endocytosed and degraded in lysosomes compared with full-length ErbB2. Altogether, we suggest that geldanamycin leads to C-terminal cleavage of ErbB2, which releases the receptor from a retention mechanism and causes endocytosis and lysosomal degradation of ErbB2.
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