p31(comet)-Induced Cell Death Is Mediated by Binding and Inactivation of Mad2
DC Field | Value | Language |
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dc.contributor.author | Shin, Hyun-Jin | - |
dc.contributor.author | Park, Eun-Ran | - |
dc.contributor.author | Yun, Sun-Hee | - |
dc.contributor.author | Kim, Su-Hyeon | - |
dc.contributor.author | Jung, Won-Hee | - |
dc.contributor.author | Woo, Seon Rang | - |
dc.contributor.author | Joo, Hyun-Yoo | - |
dc.contributor.author | Jang, Su Hwa | - |
dc.contributor.author | Chung, Hee Yong | - |
dc.contributor.author | Hong, Sung Hee | - |
dc.contributor.author | Cho, Myung-Haing | - |
dc.contributor.author | Park, Joong-Jean | - |
dc.contributor.author | Yun, Miyong | - |
dc.contributor.author | Lee, Kee-Ho | - |
dc.date.accessioned | 2021-09-04T10:45:43Z | - |
dc.date.available | 2021-09-04T10:45:43Z | - |
dc.date.created | 2021-06-10 | - |
dc.date.issued | 2015-11-06 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/91923 | - |
dc.description.abstract | Mad2, a key component of the spindle checkpoint, is closely associated with chromosomal instability and poor prognosis in cancer. p31(comet) is a Mad2-interacting protein that serves as a spindle checkpoint silencer at mitosis. In this study, we showed that p31(comet)-induced apoptosis and senescence occur via counteraction of Mad2 activity. Upon retroviral transduction of p31(comet), the majority of human cancer cell lines tested lost the ability to form colonies in a low-density seeding assay. Cancer cells with p31(comet) overexpression underwent distinct apoptosis and/or senescence, irrespective of p53 status, confirming the cytotoxicity of p31(comet). Interestingly, both cytotoxic and Mad2 binding activities were eliminated upon deletion of the C-terminal 30 amino acids of p31(comet). Point mutation or deletion of the region affecting Mad2 binding additionally abolished cytotoxic activity. Consistently, wildtype Mad2 interacting with p31(comet), but not its non-binding mutant, inhibited cell death, indicating that the mechanism of p31(comet)-induced cell death involves Mad2 inactivation. Our results clearly suggest that the regions of p31(comet) affecting interactions with Mad2, including the C-terminus, are essential for induction of cell death. The finding that p31(comet)-induced cell death is mediated by interactions with Mad2 that lead to its inactivation is potentially applicable in anticancer therapy. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | PUBLIC LIBRARY SCIENCE | - |
dc.subject | SPINDLE ASSEMBLY CHECKPOINT | - |
dc.subject | ANAPHASE-PROMOTING COMPLEX | - |
dc.subject | MITOTIC CHECKPOINT | - |
dc.subject | CHROMOSOMAL INSTABILITY | - |
dc.subject | LUNG-CANCER | - |
dc.subject | P53 GENE | - |
dc.subject | HEPATOCELLULAR-CARCINOMA | - |
dc.subject | GENOMIC INSTABILITY | - |
dc.subject | PROTEIN MAD2 | - |
dc.subject | EXPRESSION | - |
dc.title | p31(comet)-Induced Cell Death Is Mediated by Binding and Inactivation of Mad2 | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Park, Joong-Jean | - |
dc.identifier.doi | 10.1371/journal.pone.0141523 | - |
dc.identifier.scopusid | 2-s2.0-84952673830 | - |
dc.identifier.wosid | 000364398700030 | - |
dc.identifier.bibliographicCitation | PLoS One, v.10, no.11 | - |
dc.relation.isPartOf | PLoS One | - |
dc.citation.title | PLoS One | - |
dc.citation.volume | 10 | - |
dc.citation.number | 11 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | SPINDLE ASSEMBLY CHECKPOINT | - |
dc.subject.keywordPlus | ANAPHASE-PROMOTING COMPLEX | - |
dc.subject.keywordPlus | MITOTIC CHECKPOINT | - |
dc.subject.keywordPlus | CHROMOSOMAL INSTABILITY | - |
dc.subject.keywordPlus | LUNG-CANCER | - |
dc.subject.keywordPlus | P53 GENE | - |
dc.subject.keywordPlus | HEPATOCELLULAR-CARCINOMA | - |
dc.subject.keywordPlus | GENOMIC INSTABILITY | - |
dc.subject.keywordPlus | PROTEIN MAD2 | - |
dc.subject.keywordPlus | EXPRESSION | - |
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