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Chaperonin TRiC/CCT Modulates the Folding and Activity of Leukemogenic Fusion Oncoprotein AML1-ETO
DC Field | Value | Language |
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dc.contributor.author | Roh, Soung-Hun | - |
dc.contributor.author | Kasembeli, Moses | - |
dc.contributor.author | Galaz-Montoya, Jesus G. | - |
dc.contributor.author | Trnka, Mike | - |
dc.contributor.author | Lau, Wilson Chun-Yu | - |
dc.contributor.author | Burlingame, Alma | - |
dc.contributor.author | Chiu, Wah | - |
dc.contributor.author | Tweardy, David J. | - |
dc.date.accessioned | 2024-07-17T01:22:50Z | - |
dc.date.available | 2024-07-17T01:22:50Z | - |
dc.date.created | 2024-07-16 | - |
dc.date.issued | 2016-02 | - |
dc.identifier.citation | JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.291 No.9, pp.4732-4741 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | https://hdl.handle.net/10371/204731 | - |
dc.description.abstract | AML1-ETO is the most common fusion oncoprotein causing acute myeloid leukemia (AML), a disease with a 5-year survival rate of only 24%. AML1-ETO functions as a rogue transcription factor, altering the expression of genes critical for myeloid cell development and differentiation. Currently, there are no specific therapies for AML1-ETO-positive AML. While known for decades to be the translational product of a chimeric gene created by the stable chromosome translocation t(8; 21)(q22; q22), it is not known how AML1-ETO achieves its native and functional conformation or whether this process can be targeted for therapeutic benefit. Here, we show that the biosynthesis and folding of the AML1-ETO protein is facilitated by interaction with the essential eukaryotic chaperonin TRiC (or CCT). We demonstrate that a folding intermediate of AML1-ETO binds to TRiC directly, mainly through its beta-strand rich, DNA-binding domain (AML-(1-175)), with the assistance of HSP70. Our results suggest that TRiC contributes to AML1-ETO proteostasis through specific interactions between the oncoprotein's DNA-binding domain, which may be targeted for therapeutic benefit. | - |
dc.language | 영어 | - |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | - |
dc.title | Chaperonin TRiC/CCT Modulates the Folding and Activity of Leukemogenic Fusion Oncoprotein AML1-ETO | - |
dc.type | Article | - |
dc.identifier.doi | 10.1074/jbc.M115.684878 | - |
dc.citation.journaltitle | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.identifier.wosid | 000371604600039 | - |
dc.identifier.scopusid | 2-s2.0-84964636358 | - |
dc.citation.endpage | 4741 | - |
dc.citation.number | 9 | - |
dc.citation.startpage | 4732 | - |
dc.citation.volume | 291 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Roh, Soung-Hun | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | ACUTE MYELOID-LEUKEMIA | - |
dc.subject.keywordPlus | EUKARYOTIC CHAPERONIN | - |
dc.subject.keywordPlus | TRANSCRIPTION FACTOR | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | CYTOPLASMIC CHAPERONIN | - |
dc.subject.keywordPlus | INTRANUCLEAR MOBILITY | - |
dc.subject.keywordPlus | PROTEINS | - |
dc.subject.keywordPlus | COMPLEX | - |
dc.subject.keywordPlus | CCT | - |
dc.subject.keywordPlus | DOMAIN | - |
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