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In this work, we found that cisplatin is highly reactive to the RING finger domain of RNF11, a key protein involved in tumorigenesis and metastasis. The results show that cisplatin binds to RNF11 at the zinc coordination site and leads to zinc ejection from the protein. The formation of S-Pt(II) coordination and Zn(II) ions release have been confirmed by UV\u2013vis spectrometry using zinc dye and thiol agent, showing reducing the contents of thiol groups while forming S-Pt bonds and releasing zinc ions. Electrospray ionization\u2013mass spectrometry measurement indicates that each RNF11 can bind up to three platinum atoms. Kinetical analysis shows a reasonable platination rate of RNF11 with t1\/2 \u223c 3\u00a0h. CD, nuclear magnetic resonance, and gel electrophoresis measurements indicate that the cisplatin reaction causes protein unfolding and oligomerization of RNF11. Pull-down assay confirms that the platination of RNF11 interferes with the protein interaction of RNF11 with UBE2N, a key step of the functionalization of RNF11. Furthermore, Cu(I) was found to promote the platination of RNF11, which could lead to increased protein reactivity to cisplatin in tumor cells with high copper levels. These results indicate that the platination-induced zinc release of RNF11 disrupts the protein structure and interferes with its functions.<\/jats:p>","DOI":"10.1093\/mtomcs\/mfad017","type":"journal-article","created":{"date-parts":[[2023,3,12]],"date-time":"2023-03-12T00:29:12Z","timestamp":1678580952000},"source":"Crossref","is-referenced-by-count":1,"title":["Cisplatin reacts with the RING finger domain of RNF11 and interferes with the protein functions"],"prefix":"10.1093","volume":"15","author":[{"given":"Yu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Science and Technology of China , 96 Jinzhai Road, Hefei, Anhui 230026 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siming","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, Anhui 230026 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaiming","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Science and Technology of China , 96 Jinzhai Road, Hefei, Anhui 230026 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2891-7964","authenticated-orcid":false,"given":"Yangzhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Science and Technology of China , 96 Jinzhai Road, Hefei, Anhui 230026 , China"},{"name":"Department of Pharmacy, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, Anhui 230026 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,3,11]]},"reference":[{"issue":"12","key":"2024012010391394700_bib1","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1351\/pac200880122715","article-title":"\u201cPlatinum on the Road\u201d: Interactions of Antitumoral Cisplatin with Proteins","volume":"80","author":"Arnesano","year":"2008","journal-title":"Pure Appl. 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