抑制IFN-beta
中文名称
通路描述
由于细胞内dsRNA的存在作为病毒感染的信号并触发宿主干扰素（IFN）的合成，最简单的模型是病毒NS1蛋白将其dsRNA包封，从而阻止下游信号传导以激活IRF-3、NF-kB和AP-1。这些发现得到了突变分析的强力支持，表明NS1的干扰素拮抗特性取决于其结合dsRNA的能力。然而，在突变RNA结合病毒传代过程中获得的补偿性突变（S42G）导致野生型表型部分恢复，但并未恢复RNA结合能力。这表明NS1抑制IFN合成的能力并不 solely 取决于dsRNA结合，可能还涉及其他机制。
英文描述
Ligand-receptor interactions Repression of Hh signaling in the absence of ligand depends on the transmembrane receptor protein Patched (PTCH), which inhibits Smoothened (SMO) activity by an unknown mechanism. This promotes the proteolytic processing and/or degradation of the GLI family of transcription factors and maintains the pathway in a transcriptionally repressed state (reviewed in Briscoe and Therond, 2013). In the absence of ligand, PTCH is localized in the cilium, while SMO is largely concentrated in intracellular compartments. Upon binding of Hh to the PTCH receptor, PTCH is endocytosed, relieving SMO inhibition and allowing it to accumulate in the primary cilium (Marigo et al, 1996; Chen and Struhl, 1996; Stone et al, 1996; Rohatgi et al, 2007; Corbit et al, 2005; reviewed in Goetz and Anderson, 2010). In the cilium, SMO is activated by an unknown mechanism, allowing the full length transcriptional activator forms of the GLI proteins to accumulate and translocate to the nucleus, where they bind to the promoters of Hh-responsive genes (reviewed in Briscoe and Therond, 2013).
In addition to PTCH, three additional membrane proteins have been shown to bind Hh and to be required for Hh-dependent signaling in vertebrates: CDON (CAM-related/downregulated by oncogenes), BOC (brother of CDO) and GAS1 (growth arrest specific 1) (Yao et al, 2006; Okada et al, 2006; Tenzen et al, 2006; McLellan et al, 2008; reviewed in Kang et al, 2007; Beachy et al, 2010; Sanchez-Arrones et al, 2012). CDON and BOC, homologues of Drosophila Ihog and Boi respectively, are evolutionarily conserved transmembrane glycoproteins that have been shown to bind both to Hh ligand and to the canonical receptor PTCH to promote Hh signaling (Okada et al, 2006; Yao et al, 2006; Tenzen et al, 2006, McLellan et al, 2008; Izzi et al, 2011; reviewed in Sanchez-Arrones et al, 2012). Despite the evolutionary conservation, the mode of ligand binding by CDON/Ihog and BOC/Boi is distinct in vertebrates and invertebrates. High affinity ligand-binding by CDON and BOC requires Ca2+, while invertebrate ligand-binding is heparin-dependent (Okada et al, 2006; Tenzen et al, 2006; McLellan et al, 2008; Yao et al, 2006; Kavran et al, 2010). GAS1 is a vertebrate-specific GPI-anchored protein that similarly binds both to Hh ligand and to the PTCH receptor to promote Hh signaling (Martinelli and Fan, 2007; Izzi et al, 2011; reviewed in Kang et al, 2007). CDON, BOC and GAS1 have partially overlapping but not totally redundant roles, and knock-out of all three is required to abrogate Hh signaling in mice (Allen et al, 2011; Izzi et al, 2011; reviewed in Briscoe and Therond, 2013).
In addition to PTCH, three additional membrane proteins have been shown to bind Hh and to be required for Hh-dependent signaling in vertebrates: CDON (CAM-related/downregulated by oncogenes), BOC (brother of CDO) and GAS1 (growth arrest specific 1) (Yao et al, 2006; Okada et al, 2006; Tenzen et al, 2006; McLellan et al, 2008; reviewed in Kang et al, 2007; Beachy et al, 2010; Sanchez-Arrones et al, 2012). CDON and BOC, homologues of Drosophila Ihog and Boi respectively, are evolutionarily conserved transmembrane glycoproteins that have been shown to bind both to Hh ligand and to the canonical receptor PTCH to promote Hh signaling (Okada et al, 2006; Yao et al, 2006; Tenzen et al, 2006, McLellan et al, 2008; Izzi et al, 2011; reviewed in Sanchez-Arrones et al, 2012). Despite the evolutionary conservation, the mode of ligand binding by CDON/Ihog and BOC/Boi is distinct in vertebrates and invertebrates. High affinity ligand-binding by CDON and BOC requires Ca2+, while invertebrate ligand-binding is heparin-dependent (Okada et al, 2006; Tenzen et al, 2006; McLellan et al, 2008; Yao et al, 2006; Kavran et al, 2010). GAS1 is a vertebrate-specific GPI-anchored protein that similarly binds both to Hh ligand and to the PTCH receptor to promote Hh signaling (Martinelli and Fan, 2007; Izzi et al, 2011; reviewed in Kang et al, 2007). CDON, BOC and GAS1 have partially overlapping but not totally redundant roles, and knock-out of all three is required to abrogate Hh signaling in mice (Allen et al, 2011; Izzi et al, 2011; reviewed in Briscoe and Therond, 2013).
所含基因
8 个基因