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The caspase‐activated DN ase: apoptosis and beyond
Author(s) -
Larsen Brian D.,
Sørensen Claus S.
Publication year - 2017
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13970
Subject(s) - microbiology and biotechnology , signal transduction , biology , programmed cell death , apoptosis , caspase , cell growth , cell fate determination , mechanism (biology) , icad , transcription factor , genetics , philosophy , epistemology , gene
Organismal development and function requires multiple and accurate signal transduction pathways to ensure that proper balance between cell proliferation, differentiation, inactivation, and death is achieved. Cell death via apoptotic caspase signal transduction is extensively characterized and integral to this balance. Importantly, the view of apoptotic signal transduction has expanded over the previous decades. Subapoptotic caspase signaling has surfaced as mechanism that can promote the adoption of a range of cellular fates. An emerging mechanism of subapoptotic caspase signaling is the activation of the caspase‐activated DN ase ( CAD ) through controlled cleavage of the inhibitor of CAD ( ICAD ). CAD ‐induced DNA breaks incite a DNA damage response, frequently invoking p53 signaling, that transduces a change in cell fate. Cell differentiation and senescence are fates demonstrated to arise from CAD ‐induced DNA breaks. Furthermore, an apparent consequence of CAD activity is also emerging, as a potential source of oncogenic mutations. This review will discuss the mechanisms underlying CAD ‐induced DNA breaks and highlight how CAD activity promotes diverse cell fates.