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http://hdl.handle.net/123456789/1198
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DC Field | Value | Language |
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dc.contributor.author | Das, Sanjeev | - |
dc.contributor.author | Kumari, Rajni | - |
dc.contributor.author | Deshmukh, Ruhi S | - |
dc.date.accessioned | 2021-03-23T09:15:35Z | - |
dc.date.available | 2021-03-23T09:15:35Z | - |
dc.date.issued | 2019-09 | - |
dc.identifier.uri | http://hdl.handle.net/123456789/1198 | - |
dc.description.abstract | Caspase-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.iso | en | en_US |
dc.publisher | Springer Nature Limited | en_US |
dc.title | Caspase-10 inhibits ATP-citrate lyase-mediated metabolic and epigenetic reprogramming to suppress tumorigenesis | en_US |
dc.type | Article | en_US |
dc.journal | Nat Commun | en_US |
dc.volumeno | 10 | en_US |
dc.issueno | 1 | en_US |
dc.pages | 4255 | en_US |
Appears in Collections: | Molecular Oncology, Publications |
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File | Description | Size | Format | |
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s41467-019-12194-6.pdf | 2.45 MB | Adobe PDF | View/Open Request a copy |
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