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dc.contributor.authorAlbert, M-C
dc.contributor.authorBrinkmann, K
dc.contributor.authorPokrzywa, W
dc.contributor.authorGuenther, SD
dc.contributor.authorKroenke, M
dc.contributor.authorHoppe, T
dc.contributor.authorKashkar, H
dc.date.accessioned2020-11-17T03:51:03Z
dc.date.available2020-11-17T03:51:03Z
dc.date.issued2020-09-10
dc.identifierpii: 10.1038/s41419-020-02923-x
dc.identifier.citationAlbert, M. -C., Brinkmann, K., Pokrzywa, W., Guenther, S. D., Kroenke, M., Hoppe, T. & Kashkar, H. (2020). CHIP ubiquitylates NOXA and induces its lysosomal degradation in response to DNA damage. CELL DEATH & DISEASE, 11 (9), https://doi.org/10.1038/s41419-020-02923-x.
dc.identifier.issn2041-4889
dc.identifier.urihttp://hdl.handle.net/11343/251617
dc.description.abstractThe BH3-only protein NOXA is a regulator of mitochondrial apoptosis by specifically antagonizing the anti-apoptotic protein MCL-1. Here we show that the E3 ubiquitin ligase CHIP controls NOXA stability after DNA damage. Our findings reveal that CHIP and MCL-1 are binding partners of NOXA and differentially define the fate of NOXA. Whereas NOXA is initially targeted to mitochondria upon MCL-1-binding, CHIP mediates ubiquitylation of cytosolic NOXA and promotes lysosomal degradation of NOXA, which is not bound by MCL-1. Our data indicate that MCL-1 defines NOXA abundance and its pro-apoptotic activity. Increased NOXA levels beyond this threshold are effectively removed by lysosomal protein degradation triggered via CHIP-mediated ubiquitylation. Together, these results shed new light on regulatory circuits controlling DNA damage response and identified the E3 ligase CHIP as a new molecular guardian, which restricts the cytosolic accumulation of NOXA upon genotoxic stress.
dc.languageEnglish
dc.publisherSPRINGERNATURE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleCHIP ubiquitylates NOXA and induces its lysosomal degradation in response to DNA damage
dc.typeJournal Article
dc.identifier.doi10.1038/s41419-020-02923-x
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titleCell Death and Disease
melbourne.source.volume11
melbourne.source.issue9
dc.rights.licenseCC BY
melbourne.elementsid1466300
melbourne.contributor.authorBrinkmann, Kerstin
dc.identifier.eissn2041-4889
melbourne.accessrightsOpen Access


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