Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/1198
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dc.contributor.authorDas, Sanjeev-
dc.contributor.authorKumari, Rajni-
dc.contributor.authorDeshmukh, Ruhi S-
dc.date.accessioned2021-03-23T09:15:35Z-
dc.date.available2021-03-23T09:15:35Z-
dc.date.issued2019-09-
dc.identifier.urihttp://hdl.handle.net/123456789/1198-
dc.description.abstractCaspase-10 belongs to the class of initiator caspases and is a close homolog of caspase-8. However, the lack of caspase-10 in mice and limited substrate repertoire restricts the understanding of its physiological functions. Here, we report that ATP-citrate lyase (ACLY) is a caspase-10 substrate. Caspase-10 cleaves ACLY at the conserved Asp1026 site under conditions of altered metabolic homeostasis. Cleavage of ACLY abrogates its enzymatic activity and suppresses the generation of acetyl-CoA, which is critical for lipogenesis and histone acetylation. Thus, caspase-10-mediated ACLY cleavage results in reduced intracellular lipid levels and represses GCN5-mediated histone H3 and H4 acetylation. Furthermore, decline in GCN5 activity alters the epigenetic profile, resulting in downregulation of proliferative and metastatic genes. Thus caspase-10 suppresses ACLY-promoted malignant phenotype. These findings expand the substrate repertoire of caspase-10 and highlight its pivotal role in inhibiting tumorigenesis through metabolic and epigenetic mechanisms.en_US
dc.language.isoenen_US
dc.publisherSpringer Nature Limiteden_US
dc.titleCaspase-10 inhibits ATP-citrate lyase-mediated metabolic and epigenetic reprogramming to suppress tumorigenesisen_US
dc.typeArticleen_US
dc.journalNat Communen_US
dc.volumeno10en_US
dc.issueno1en_US
dc.pages4255en_US
Appears in Collections:Molecular Oncology, Publications

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