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Cells must maintain zinc homeostasis to effectively respond to DNA damage caused by various stressful stimuli. Members of the Zrt\u2010, Irt\u2010related protein (ZIP) family are recognized as key regulators of intracellular zinc levels. Dysfunction of ZIPs has been associated with numerous diseases, including cancer, cardiovascular diseases, and neurodegenerative disorders. In the present study, human bronchial epithelial BEAS\u20102B cells were used to investigate the response of ZIPs to bleomycin, a well\u2010known antibiotic that induces DNA damage. Among the ZIPs that exhibited altered expression following bleomycin treatment, ZIP1 showed the most prompt and significant induction. Both knockdown and overexpression experiments demonstrated that ZIP1 plays a crucial role in the cellular response to DNA damage. Mechanistically, we found that the level of TNF\u03b1 was upregulated in bleomycin\u2010treated cells, and inhibiting this cytokine reduced the induction effect of ZIP1 caused by bleomycin. Additionally, we observed an increase in the accumulation of NF\u2010\u03baB in the cell nuclei, and inhibition of NF\u2010\u03baB also diminished the effect of bleomycin on ZIP1. Two NF\u2010\u03baB binding sites were identified in the upstream sequence of\n                    <jats:italic>SLC39A1<\/jats:italic>\n                    , the gene that encodes ZIP1. The application of bleomycin significantly enhanced the binding of NF\u2010\u03baB to these specific sites. Taken together, our study reveals that bleomycin treatment may activate the TNF\u03b1\u2010NF\u2010\u03baB pathway, which in turn upregulates ZIP1, helping cells better cope with the DNA damage induced by this antibiotic.\n                  <\/jats:p>","DOI":"10.1096\/fj.202602997r","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T16:00:30Z","timestamp":1786723230000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>ZIP1<\/scp>\n                    Is a Critical\n                    <scp>DNA<\/scp>\n                    Damage\u2010Responsive Zinc Transporter Induced by Bleomycin via the\n                    <scp>TNF\u03b1<\/scp>\n                    \u2013\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    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