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Adelson Medical Research Foundation","doi-asserted-by":"publisher","award":["86493811"],"award-info":[{"award-number":["86493811"]}],"id":[{"id":"10.13039\/100005984","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,10,22]]},"abstract":"<jats:p>Liquid\u2013liquid phase separation has emerged as a crucial mechanism driving the formation of membraneless biomolecular condensates, which play important roles in numerous cellular processes. These condensates, found both in the nucleus and cytoplasm, are formed through multivalent, low-affinity interactions between various molecules. P62-containing condensates serve, among other functions, as proteolytic hubs for the ubiquitin\u2013proteasome system. In this study, we investigated the dynamic interplay between nuclear p62 condensates and promyelocytic nuclear bodies (PML-NBs). We show that p62 condensates stabilize PML-NBs under both basal conditions and following exposure to arsenic trioxide which stimulates their degradation. We further show that this effect on the stability of PML-NBs is due to sequestration of their ubiquitin E3 ligase RNF4 in the p62 condensates with subsequent rapid degradation of the ligase. The sequestration of the ligase is made possible by association between the proline-rich domain of the PML protein and the PB1 domain of p62, which results in the formation of a PML-NB shell around the p62 condensates. Importantly, these hybrid structures do not undergo fusion and mixing of their contents which leaves unsolved the mechanism of sequestration of RNF4 in the condensates. These findings suggest an additional possible mechanism of PML-NB as a tumor suppressor which is mediated via interactions between different biomolecular condensates.<\/jats:p>","DOI":"10.1073\/pnas.2414377121","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T13:34:31Z","timestamp":1729172071000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["Nuclear p62 condensates stabilize the promyelocytic leukemia nuclear bodies by sequestering their ubiquitin ligase RNF4"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4583-5533","authenticated-orcid":false,"given":"Afu","family":"Fu","sequence":"first","affiliation":[{"name":"Rappaport-Technion Integrated Cancer Center, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 3109602, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1400-1437","authenticated-orcid":false,"given":"Zhiwen","family":"Luo","sequence":"additional","affiliation":[{"name":"Rappaport-Technion Integrated Cancer Center, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 3109602, Israel"},{"name":"Department of Hepatobiliary Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Ziv","sequence":"additional","affiliation":[{"name":"Smoler Proteomic Center and Faculty of Biology, Technion-Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4011-0939","authenticated-orcid":false,"given":"Xinyu","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Lulu-Shimron","sequence":"additional","affiliation":[{"name":"Rappaport-Technion Integrated Cancer Center, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 3109602, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Cohen-Kaplan","sequence":"additional","affiliation":[{"name":"Rappaport-Technion Integrated Cancer Center, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 3109602, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9184-8944","authenticated-orcid":false,"given":"Aaron","family":"Ciechanover","sequence":"additional","affiliation":[{"name":"Rappaport-Technion Integrated Cancer Center, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 3109602, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.035"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevFluids.4.110506"},{"key":"e_1_3_4_3_2","first-page":"3766","article-title":"Liquid-liquid phase separation (LLPS) in cellular physiology and tumor biology","volume":"11","author":"Peng P.-H.","year":"2021","unstructured":"P.-H. 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