{"doi":"10.17615/91nr-g209","title":"Zinc-induced PTEN Protein Degradation through the Proteasome Pathway in Human Airway Epithelial Cells","abstract":"The tumor suppressor PTEN is a putative negative regulator of the phosphatidylinositol 3-kinase/Akt pathway. Exposure to Zn2+ ions induces Akt activation, suggesting that PTEN may be modulated in this process. Therefore, the effects of Zn2+ on PTEN were studied in human airway epithelial cells and rat lungs. Treatment with Zn2+ resulted in a significant reduction in levels of PTEN protein in a dose- and time-dependent fashion in a human airway epithelial cell line. This effect of Zn2+was also observed in normal human airway epithelial cells in primary culture and in rat airway epithelium in vivo. Concomitantly, levels of PTEN mRNA were also significantly reduced by Zn2+ exposure. PTEN phosphatase activity evaluated by measuring Akt phosphorylation decreased after Zn2+ treatment. Pretreatment of the cells with a proteasome inhibitor significantly blocked zinc-induced reduction of PTEN protein as well as the increase in Akt phosphorylation, implicating the involvement of proteasome-mediated PTEN degradation. Further study revealed that Zn2+-induced ubiquitination of PTEN protein may mediate this process. A phosphatidylinositol 3-kinase inhibitor blocked PTEN degradation induced by Zn2+, suggesting that phosphatidylinositol 3-kinase may participate in the regulation of PTEN. However, both the proteasome inhibitor and phosphatidylinositol 3-kinase inhibitor failed to prevent significant down-regulation of PTEN mRNA expression in response to Zn2+. In summary, exposure to Zn2+ ions causes PTEN degradation and loss of function, which is mediated by an ubiquitin-associated proteolytic process in the airway epithelium.","journal":"UNC Libraries","year":2021,"id":208766,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":105507,"name":"Andrew J. Ghio","orcid":"0000-0003-0502-6448","position":1,"is_corresponding":false},{"id":795422,"name":"Wenli Zhang","orcid":"0000-0002-6243-6286","position":2,"is_corresponding":false},{"id":348847,"name":"William Reed","orcid":"0000-0002-4580-485X","position":3,"is_corresponding":false},{"id":354013,"name":"Young E. Whang","orcid":"0000-0002-1621-6661","position":4,"is_corresponding":false},{"id":795423,"name":"Weidong Wu","orcid":"0000-0002-7334-8679","position":5,"is_corresponding":false},{"id":548647,"name":"James M. Samet","orcid":"0000-0002-4053-9022","position":6,"is_corresponding":false},{"id":795421,"name":"Xinchao Wang","orcid":"0000-0002-5224-6286","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:51:57.582057Z","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":[]}