ArticleCell death & disease2014
Identification of prolidase as a high affinity ligand of the ErbB2 receptor and its regulation of ErbB2 signaling and cell growth.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- A degrader of HER2 and EGFR abolishes p95HER2 and shows robust antitumor efficacy in HER2-positive breast cancer.Scientific reports · 2026Article
- Targeted dual degradation of HER2 and EGFR obliterates oncogenic signaling, overcomes therapy resistance, and inhibits metastatic lesions in HER2-positive breast cancer models.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Article
- Targeting Epidermal Growth Factor Receptor for Cancer Treatment: Abolishing Both Kinase-Dependent and Kinase-Independent Functions of the Receptor.Pharmacological reviews · 2023Review
- Article
- Depleting receptor tyrosine kinases EGFR and HER2 overcomes resistance to EGFR inhibitors in colorectal cancer.Journal of experimental & clinical cancer research : CR · 2022Article
- Dysregulation of macrophage PEPD in obesity determines adipose tissue fibro-inflammation and insulin resistance.Nature metabolism · 2022Article
- Loss of peptidase D binding restores the tumor suppressor functions of oncogenic p53 mutants.Communications biology · 2021Article
- The root cause of drug resistance in HER2-positive breast cancer and the therapeutic approaches to overcoming the resistance.Pharmacology & therapeutics · 2021Review
- PROLIDASE: A Review from Discovery to its Role in Health and Disease.Frontiers in molecular biosciences · 2021Review
- Current Understanding of the Emerging Role of Prolidase in Cellular Metabolism.International journal of molecular sciences · 2020Review
- A recombinant human protein targeting HER2 overcomes drug resistance in HER2-positive breast cancer.Science translational medicine · 2019Article
- PEPD is a pivotal regulator of p53 tumor suppressor.Nature communications · 2017Article
- ErbB2 regulates autophagic flux to modulate the proteostasis of APP-CTFs in Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The role of MAPK signaling pathway in the Her-2-positive meningiomas.Oncology reports · 2016Article
- Dual inhibition of ErbB1 and ErbB2 in cancer by recombinant human prolidase mutant hPEPD-G278D.Oncotarget · 2016Article
- A plasma proteolysis pathway comprising blood coagulation proteases.Oncotarget · 2016Article
- Inhibition of ERBB2-overexpressing Tumors by Recombinant Human Prolidase and Its Enzymatically Inactive Mutant.EBioMedicine · 2015Article
- The HER2 Signaling Network in Breast Cancer--Like a Spider in its Web.Journal of mammary gland biology and neoplasia · 2014Review
- Prolidase is required for early trafficking events during influenza A virus entry.Journal of virology · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
ErbB2, an important membrane-bound receptor tyrosine kinase, was discovered nearly 30 years ago, but a natural ligand has never been found previously. ErbB2 is also an important oncogene and anticancer target, and its overexpression in cancer is associated with poor disease prognosis. Here, we report that human prolidase (PEPD) is a high affinity ligand of ErbB2 and binds as a homodimer to subdomain 3 in the extracellular domain of this receptor. In ErbB2-overexpressing cells, both ErbB2 monomers and activated dimers exist. PEPD bound to ErbB2 monomers relatively slowly but caused ErbB2 dimerization, ErbB2 phosphorylation and downstream signaling. In contrast, PEPD bound rapidly to ErbB2 homodimers and rapidly silenced ErbB2 dimer-Src signaling, a key oncogenic pathway of ErbB2, by disrupting the association of Src with ErbB2. PEPD also caused pronounced ErbB2 depletion, resulting from ErbB2 internalization and degradation. Moreover, PEPD strongly inhibited the DNA synthesis, anchorage-independent growth and invasion and migration of cells that overexpressed ErbB2 but had no effect on cells without ErbB2 overexpression. Cells became sensitized to PEPD upon achieving stable ErbB2 overexpression. Thus, the impact of PEPD on ErbB2 is predominantly inhibitory, and PEPD targets cells addicted to ErbB2. PEPD is also a dipeptidase, but its enzymatic function is not involved in ErbB2 modulation. These findings revise our understanding of ErbB2 and PEPD and may be especially important for combating ErbB2-positive cancers.
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Registered trials
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.