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Updated: Apr 7, 2026

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Published on: March 24, 2017
Cellular FLICE-Inhibitory Protein Regulates Tissue Homeostasis
Hiroyasu Nakano1, Xuehua Piao2, Ryodai Shindo2,3
1Department of Biochemistry, Toho University School of Medicine, 5-21-16 Omori-Nishi, Ota-Ku, Tokyo, 143-8540, Japan. hiroyasu.nakano@med.toho-u.ac.jp.
Abstract:
Cellular FLICE-inhibitory protein (cFLIP) is structurally related to caspase-8, but lacks its protease activity. Cflip gene encodes several splicing variants including short form (cFLIPs) and long form (cFLIPL). cFLIPL is composed of two death effector domains at the N terminus and a C-terminal caspase-like domain, and cFLIPs lacks the caspase-like domain. Our studies reveal that cFLIP plays a central role in NF-κB-dependent survival signals that control apoptosis and programmed necrosis. Germline deletion of Cflip results in embryonic lethality due to enhanced apoptosis and programmed necrosis; however, the combined deletion of the death-signaling regulators, Fadd and Ripk3, prevents embryonic lethality in Cflip-deficient mice. Moreover, tissue-specific deletion of Cflip reveals cFLIP as a crucial regulator that maintains tissue homeostasis of immune cells, hepatocytes, intestinal epithelial cells, and epidermal cells by preventing apoptosis and programmed necrosis.
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