PCGF2 negatively regulates arsenic trioxide-induced PML-RARA protein degradation via UBE2I inhibition in NB4 cells
DC Field | Value | Language |
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dc.contributor.author | Jo, Sungsin | - |
dc.contributor.author | Lee, Young Lim | - |
dc.contributor.author | Kim, Sojin | - |
dc.contributor.author | Lee, Hongki | - |
dc.contributor.author | Chung, Heekyoung | - |
dc.date.accessioned | 2022-07-15T14:31:03Z | - |
dc.date.available | 2022-07-15T14:31:03Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2016-07 | - |
dc.identifier.issn | 0167-4889 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/154306 | - |
dc.description.abstract | Arsenic trioxide (ATO) is a therapeutic agent for acute promyelocytic leukemia (APL) which induces PML-RARA protein degradation via enhanced UBE2I-mediated sumoylation. PCGF2, a Polycomb group protein, has been suggested as an anti-SUMO E3 protein by inhibiting the sumoylation of UBE2I substrates, HSF2 and RANGAP1, via direct interaction. Thus, we hypothesized that PCGF2 might play a role in ATO-induced PML-RARA degradation by interacting with UBE2I. PCGF2 protein was down-regulated upon ATO treatment in human APL cell line, NB4. Knockdown of PCGF2 in NB4 cells, in the absence of ATO treatment, was sufficient to induce sumoylation-, ubiquitylation- and PML nuclear body-mediated degradation of PML-RARA protein. Moreover, overexpression of PCGF2 protected ATO-mediated degradation of ectopic and endogenous PML-RARA in 293T and NB4 cells, respectively. In 293T cells, UBE2I-mediated PML-RARA degradation was reduced upon PCGF2 co-expression. In addition, UBE2I-mediated sumoylation of PML-RARA was reduced upon PCGF2 co-expression and PCGF2-UBE2I interaction was confirmed by co-immunoprecipitation. Likewise, endogenous PCGF2-UBE2I interaction was detected by co-immunoprecipitation and immunofluorescence assays in NB4 cells. Intriguingly, upon ATO-treatment, such interaction was disrupted and UBE2I was co-immunoprecipitated or co-localized with its SUMO substrate, PML-RARA. Taken together, our results suggested a novel role of PCGF2 in ATO-mediated degradation of PML-RARA that PCGF2 might act as a negative regulator of UBE2I via direct interaction. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER SCIENCE BV | - |
dc.title | PCGF2 negatively regulates arsenic trioxide-induced PML-RARA protein degradation via UBE2I inhibition in NB4 cells | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Chung, Heekyoung | - |
dc.identifier.doi | 10.1016/j.bbamcr.2016.03.019 | - |
dc.identifier.scopusid | 2-s2.0-84964378368 | - |
dc.identifier.wosid | 000378360200004 | - |
dc.identifier.bibliographicCitation | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v.1863, no.7, pp.1499 - 1509 | - |
dc.relation.isPartOf | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | - |
dc.citation.title | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | - |
dc.citation.volume | 1863 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 1499 | - |
dc.citation.endPage | 1509 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | ACUTE PROMYELOCYTIC LEUKEMIA | - |
dc.subject.keywordPlus | ALPHA ONCOPROTEIN | - |
dc.subject.keywordPlus | MEL-18 INTERACTS | - |
dc.subject.keywordPlus | NUCLEAR-BODIES | - |
dc.subject.keywordPlus | RETINOIC ACID | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | SUMO | - |
dc.subject.keywordPlus | METHYLATION | - |
dc.subject.keywordPlus | UBIQUITIN | - |
dc.subject.keywordPlus | TRANSFORMATION | - |
dc.subject.keywordAuthor | Arsenic trioxide | - |
dc.subject.keywordAuthor | PCGF2 | - |
dc.subject.keywordAuthor | UBE2I | - |
dc.subject.keywordAuthor | PML-RARA | - |
dc.subject.keywordAuthor | Protein degradation | - |
dc.subject.keywordAuthor | Sumoylation | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0167488916300726?via%3Dihub | - |
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