title: Cellular FLICE-Inhibitory Protein Regulates Tissue Homeostasis.
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). cFLIPLis 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.
authors.affiliation: 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.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Nakano
authors.affiliation: Department of Biochemistry, Toho University School of Medicine, 5-21-16 Omori-Nishi, Ota-Ku, Tokyo, 143-8540, Japan.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Piao
authors.affiliation: Department of Biochemistry, Toho University School of Medicine, 5-21-16 Omori-Nishi, Ota-Ku, Tokyo, 143-8540, Japan.|Department of Immunology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan.
authors.forename: Ryodai
authors.initials: R
authors.lastname: Shindo
authors.affiliation: Department of Biochemistry, Toho University School of Medicine, 5-21-16 Omori-Nishi, Ota-Ku, Tokyo, 143-8540, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Komazawa-Sakon
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053181:Caspase 8 / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016328:NF-kappa B; D053181:Caspase 8