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Curr Top Microbiol Immunol. 2017;403:119-141. doi: 10.1007/82_2015_448.

Cellular FLICE-Inhibitory Protein Regulates Tissue Homeostasis.

Author information

1
Department 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.
2
Department of Biochemistry, Toho University School of Medicine, 5-21-16 Omori-Nishi, Ota-Ku, Tokyo, 143-8540, Japan.
3
Department of Immunology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan.

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.

PMID:
26160013
DOI:
10.1007/82_2015_448
[Indexed for MEDLINE]

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