{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:18:33Z","timestamp":1785421113077,"version":"3.56.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24H01381"],"award-info":[{"award-number":["24H01381"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24H02286"],"award-info":[{"award-number":["24H02286"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24H02283"],"award-info":[{"award-number":["24H02283"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22H04996"],"award-info":[{"award-number":["22H04996"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JPMJCR21E6"],"award-info":[{"award-number":["JPMJCR21E6"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009665","name":"Vehicle Racing Commemorative Foundation","doi-asserted-by":"publisher","award":["6296"],"award-info":[{"award-number":["6296"]}],"id":[{"id":"10.13039\/100009665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009665","name":"Vehicle Racing Commemorative Foundation","doi-asserted-by":"publisher","award":["6296"],"award-info":[{"award-number":["6296"]}],"id":[{"id":"10.13039\/100009665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,6,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Chromosomal instability is a common feature of malignancies that arises from persistent defects in chromosome segregation during mitosis. The resulting genetic heterogeneity and acquired malignant traits often characterize advanced disease. However, little is known about the mitotic processes underlying the acquisition of chromosomal instability and whether or how they might contribute to the early stages of cancer initiation. Here, we focused on a characteristic chromosome congression defect termed ECAC (Ectopic Chromosome Around Centrosome), which is observed in human papillomavirus (HPV)-positive cervical dysplasia, a premalignant lesion of the cervix. The expression of the HPV oncoprotein E6 induced proteasome-dependent degradation of the kinetochore motor CENP-E in addition to p53. We then identified the region of CENP-E required for E6-dependent degradation and conducted rescue experiments using a degradation-resistant mutant. These experiments demonstrated that CENP-E degradation is the main cause of the ECAC phenotype. Remarkably, the E6-mediated CENP-E destabilization and the resulting induction of ECAC were observed across multiple high-risk HPV genotypes, indicating that these defects represent a broadly shared pathological feature of oncogenic HPV infection. We also found that sustained E6 expression led to the accumulation of aneuploid cell populations during long-term culture. These findings define the molecular basis of ECAC and suggest that persistent chromosome congression defects can initiate chromosomal instability in premalignant cervical lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>High-risk human papillomaviruses (HPVs) drive epithelial carcinogenesis through the viral oncoproteins E6 and E7, primarily by disrupting p53- and RB-dependent pathways. While HPV16 E6 has been implicated in chromosome congression defects through destabilization of the mitotic motor CENP-E, it has remained unclear whether CENP-E destabilization is sufficient to induce such defects and whether they are shared across multiple high-risk HPV genotypes. Here, we show in cultured cell models that a degradation-resistant CENP-E mutant suppresses E6-mediated chromosome congression defects and that this mitotic phenotype is consistently observed in cells expressing E6 proteins from multiple high-risk HPV genotypes. Persistence of this mitotic abnormality leads to the accumulation of aneuploid cell populations. These findings link the E6-CENP-E axis to a characteristic mitotic defect in cervical premalignant lesions and suggest that this mitotic abnormality may contribute to the acquisition of chromosomal instability and the development of cervical cancers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00625-26","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:00:59Z","timestamp":1779886859000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["High-risk HPV E6 induces an aneuploidy-prone chromosome congression defect through destabilization of CENP-E"],"prefix":"10.1128","volume":"100","author":[{"given":"Nanami","family":"Seshimo","sequence":"first","affiliation":[{"name":"Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research","place":["Tokyo, Japan"]},{"id":[{"id":"https:\/\/ror.org\/022cvpj02","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Diagnostic Pathology, The University of Tokyo Hospital","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Hori","sequence":"additional","affiliation":[{"name":"Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiko","family":"Furuta","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00f2txz25","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Clinical Cytology, Department of Medical Laboratory Sciences, School of Allied Health Sciences, Kitasato University","place":["Kanagawa, Japan"]},{"name":"Division of Pathology, Cancer Institute of the Japanese Foundation for Cancer Research","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Hirota","sequence":"additional","affiliation":[{"name":"Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6609-2436","authenticated-orcid":true,"given":"Ryu-Suke","family":"Nozawa","sequence":"additional","affiliation":[{"name":"Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12625"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2016.06.002"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2016.10.023"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-024-00761-7"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14989"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15544"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2014.12.028"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021641"},{"key":"e_1_3_3_10_2","first-page":"497","article-title":"Human papillomavirus and the three group metaphase figure as markers of an increased risk for the development of cervical carcinoma","volume":"140","author":"Claas EC","year":"1992","unstructured":"Claas EC, Quint WG, Pieters WJ, Burger MP, Oosterhuis WJ, Lindeman J. 1992. 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