ArticleCell stress & chaperones2010
Geldanamycin selectively targets the nascent form of ERBB3 for degradation.
Article in Cell stress & chaperones, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- A multicenter trial evaluating retaspimycin HCL (IPI-504) plus trastuzumab in patients with advanced or metastatic HER2-positive breast cancer.Breast cancer research and treatment · 2013Trial
- ATP-Driven Nonequilibrium Activation of Kinase Clients by the Molecular Chaperone Hsp90.Biophysical journal · 2020Article
- Combined BRAF and HSP90 Inhibition in Patients with UnresectableClinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Article
- Targeting HER2 by Combination Therapies.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Article
- How Hsp90 and Cdc37 Lubricate Kinase Molecular Switches.Trends in biochemical sciences · 2017Review
- HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death.Cell death & disease · 2016Article
- Targeting HER3 by interfering with its Sec61-mediated cotranslational insertion into the endoplasmic reticulum.Oncogene · 2015Article
- Targeting Hsp90 in urothelial carcinoma.Oncotarget · 2015Review
- Phosphorylated and unphosphorylated serine 13 of CDC37 stabilize distinct interactions between its client and HSP90 binding domains.Biochemistry · 2015Article
- Anti-tumor activity of WK88-1, a novel geldanamycin derivative, in gefitinib-resistant non-small cell lung cancers with Met amplification.Cancer science · 2014Article
- High-throughput screening identifies aclacinomycin as a radiosensitizer of EGFR-mutant non-small cell lung cancer.Translational oncology · 2013Article
- E3 ubiquitin ligases in ErbB receptor quantity control.Seminars in cell & developmental biology · 2010Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Heat shock protein 90 (HSP90) targets a broad spectrum of client proteins with divergent modes of interaction and consequences. The homologous epidermal growth factor receptor (EGFR) and ERBB2 receptors as well as kinase-deficient mutants thereof differ in their requirement for HSP90 in the nascent versus mature state of the receptor. Specific features of the kinase domain have been implicated for the selective association of HSP90 with mature ERBB2. We evaluated the role of HSP90 for the homologous ERBB3 receptor. ERBB3 is naturally kinase deficient, a central mediator in cell survival and stress response and the primary dimerization partner for ERBB2 in signaling. Cellular studies indicate that, similar to EGFR, the geldanamycin (GA) sensitivity of ERBB3 and HSP90 binding resides in the nascent state and is dependent on the presence of the kinase domain of ERBB3. Furthermore, despite its intrinsic lack of kinase activity and in contrast to the reported GA sensitivity of mature and kinase-deficient EGFR, the GA sensitivity of the nascent state of ERBB3 appears to be exclusive. Geldanamycin disrupts the interaction of ERBB3 and HSP90 and inhibits ERBB3 maturation at an early stage of synthesis, prior to export from the ER. Studies with a photo-convertible fusion protein of ERBB3 suggest geldanamycin sensitivity at a later stage in maturation, possibly through the putative role of HSP90 in structural proofreading.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.