Backbone and side-chain chemical shift assignments of a cellular FLICE-inhibitory protein (c-FLIP S )
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ARTICLE
Backbone and side‑chain chemical shift assignments of a cellular FLICE‑inhibitory protein (c‑FLIPS) Zhi‑Qiang Bai1,2,3 · Bin Liu1,3 · Xiaofang Ma2 · Kaifeng Hu1,2 Received: 4 February 2020 / Accepted: 29 May 2020 © Springer Nature B.V. 2020
Abstract Cellular FLICE-inhibitory protein (c-FLIP), which is involved in regulating the apoptosis of the extrinsic cell death pathway contains two death effector domains (DED). There are several splicing variants including short-form (c-FLIPS) and long-form (c-FLIPL). The death-inducing signaling complex (DISC) initiates apoptosis and programmed necrosis, DISC assembly and activation are regulated by c-FLIP. Here we report the NMR chemical shift assignments of c-FLIPs, which pave the way for investigating the molecular basis of the anti-apoptotic function of c-FLIPS. Keywords Apoptosis · c-FLIPS · NMR
Biological context Apoptosis is an ordered cell-intrinsic suicide program and serves as an efficient cellular quality control mechanism that removes unwanted cells from the organism. (Riedl and Salvesen 2007; Steller 1995). The formation of the apoptosome and death-inducing signaling complex (DISC) regulates cell death (Li et al. 2006; Riedl and Salvesen 2007). The DISC complex comprises the receptor Fas (CD95), the adaptor protein Fas-associated death domain (FADD), the initiator procaspase-8/FLICE (FADD-like interleukin-1βconverting enzyme), procaspase-10, and cellular FLICEinhibitory protein (c-FLIP) (Lavrik et al. 2005; Lavrik and Krammer 2012). c-FLIP plays a crucial role in the regulation of death receptor-induced apoptosis during the early stages of death receptor signaling, maintaining tissue homeostasis of * Kaifeng Hu [email protected] 1
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, 132 Lanhei Road, Heilongtan, Kunming 650201, Yunnan, People’s Republic of China
2
Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
3
University of Chinese Academy of Sciences, Beijing 100049, China
immune cells, intestinal epithelial cells, hepatocytes, and epidermal cells by preventing apoptosis and programmed necrosis (Nakano et al. 2017). Overexpression of c-FLIP has been identified in many different tumour types, and its downregulation has been shown to restore apoptosis mediated by CD95 signaling pathway (Shirley and Micheau 2013). Hence, suppression of c-FLIP in tumor cells to enhance apoptosis is an important means for cancer therapy (Safa 2013). Three splice forms of c-FLIP have been identified: a longform (c-FLIPL) and two short forms (c-FLIPS, and c-FLIPR) (Golks et al. 2005; Irmler et al. 1997). c-FLIPL is highly homologous to procaspases-8 and -10, possessing tandem death effector domains (DED) at its N-terminus and a catalytically inactive protease-like domain at its C-terminus (Yu et al. 2009). c-FLIPL is ubiquitously expressed in various tissues, whereas c-FLIPS is expressed rather
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