{"doi":"10.1038/cr.2011.75","title":"Proteostasis regulation at the endoplasmic reticulum: a new perturbation site for targeted cancer therapy","abstract":null,"journal":"Cell Research","year":2011,"id":47113,"datarank":5.176395078778473,"base_score":4.718498871295094,"endowment":4.718498871295094,"self_citation_contribution":0.7077748306942643,"citation_network_contribution":4.468620248084209,"self_endowment_contribution":0.7077748306942643,"citer_contribution":4.468620248084209,"corpus_percentile":null,"corpus_rank":null,"citation_count":111,"citer_count":104,"citers_with_citation_signal":97,"citers_with_endowment":97,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":145321,"name":"Yihong Ye","orcid":null,"position":1,"is_corresponding":false},{"id":217573,"name":"Yanfen Liu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Proteostasis regulation at the endoplasmic reticulum: a new perturbation site for targeted cancer therapy","abstract":"To deal with the constant challenge of protein misfolding in the endoplasmic reticulum (ER), eukaryotic cells have evolved an ER protein quality control (ERQC) mechanism that is integrated with an adaptive stress response. The ERQC pathway is comprised of factors residing in the ER lumen that function in the identification and retention of aberrantly folded proteins, factors in the ER membrane for retrotranslocation of misfolded polypeptides, and enzymes in the cytosol that degrade retrotranslocated proteins. The integrated stress response (termed ER stress or unfolded protein response, UPR) contains several signaling branches elicited from the ER membrane, which fine-tune the rate of protein synthesis and entry into the ER to match the ER folding capacity. The fitness of the cell, particularly those bearing a high secretory burden, is critically dependent on functional integrity of the ER, which in turn relies on these stress-attenuating mechanisms to maintain protein homeostasis, or proteostasis. Aberrant proteostasis can trigger cellular apoptosis, making these adaptive stress response systems attractive targets for perturbation in treatment of cell malignancies. Here, we review our current understanding of how the cell preserves ER proteostasis and discuss how we may harness the mechanistic information on this process to develop new cancer therapeutics.","is_dataset_classified":null,"base_score":4.718498871295094,"endowment":4.718498871295094,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21537343","pmcid":"PMC3203708","openalex_id":"https://openalex.org/W2066557401","authors":[],"funders":[{"funder_name":"Intramural NIH HHS","grant_id":"","title":null},{"funder_name":"Intramural NIH HHS","grant_id":"","title":null}],"total_grants":2,"fwci":4.0437,"citation_percentile":0.94282681,"influential_citations":3,"citation_trend":[{"year":2012,"count":12},{"year":2013,"count":11},{"year":2014,"count":8},{"year":2015,"count":8},{"year":2016,"count":10},{"year":2017,"count":4},{"year":2018,"count":4},{"year":2019,"count":10},{"year":2020,"count":9},{"year":2021,"count":8},{"year":2022,"count":6},{"year":2023,"count":7},{"year":2024,"count":3},{"year":2025,"count":6},{"year":2026,"count":4}],"oa_status":"bronze","license":"https://www.springer.com/tdm","oa_locations":[{"url":"https://www.nature.com/articles/cr201175.pdf","host_type":"journal"},{"url":"https://www.nature.com/articles/cr201175.pdf","host_type":"BRONZE"},{"url":"https://www.nature.com/articles/cr201175.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/cr201175","host_type":"publisher"},{"url":"https://doi.org/10.1038/cr.2011.75","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21537343","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3203708","host_type":"repository"}],"fields_of_study":["Endoplasmic Reticulum Stress and Disease","Autophagy in Disease and Therapy","Fungal and yeast genetics research","Biology","Medicine","Animals","Antineoplastic Agents","Endoplasmic Reticulum","Glycoproteins","Humans","Intracellular Signaling Peptides and Proteins","Molecular Targeted Therapy","Neoplasms","Proteasome Endopeptidase Complex","Proteasome Inhibitors","Protein Processing, Post-Translational","Protein Transport","Proteins","Stress, Physiological","Ubiquitination","Unfolded Protein Response"],"mesh_terms":["Animals","Antineoplastic Agents","Endoplasmic Reticulum","Glycoproteins","Humans","Neoplasms","Protein Processing, Post-Translational","Proteins","Stress, Physiological","Protein Transport","Proteasome Endopeptidase Complex","Intracellular Signaling Peptides and Proteins","Ubiquitination","Unfolded Protein Response","Molecular Targeted Therapy","Proteasome Inhibitors"],"keywords":["Proteostasis","Endoplasmic reticulum","Unfolded protein response","Cell biology","Protein folding","Endoplasmic-reticulum-associated protein degradation","Biology","Secretory pathway","Crosstalk","Golgi apparatus"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.24104200.v1","title":"Additional file 1 of Ajugol's upregulation of TFEB-mediated autophagy alleviates endoplasmic reticulum stress in chondrocytes and retards osteoarthritis progression in a mouse model","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.24104200","title":"Additional file 1 of Ajugol's upregulation of TFEB-mediated autophagy alleviates endoplasmic reticulum stress in chondrocytes and retards osteoarthritis progression in a mouse model","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-17T02:20:53.705803Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}