NLRP3 炎症小体
中文名称
通路描述
NLRP3（Cryopyrin）炎症小体是目前研究最透彻的。它由 NLRP3、ASC（PYCARD）和procaspase-1 组成；CARD8（Cardinal）也被认为是其组成部分之一。它受到多种病原体、细菌毒素以及多种 PAMPs、DAMPs（如透明质酸和尿酸）和异源性刺激物（如二氧化硅和石棉）的激活（参见 Schroder & Tschopp, 2010 表 S1）。NLRP3 突变导致持续激活与 Muckle-Wells 综合征、家族性冷性自身免疫综合征和 NOMID（Ting et al. 2006）等人类疾病相关，这些疾病表现为皮疹和其他与全身性炎症相关的症状。这些症状的成因是失控的 IL-1β产生。多项研究表明，NLRP3 炎症小体由颗粒激活剂（如 Hornung et al. 2008）激活需要吞噬作用，但这对于 ATP 的反应（由 P2X7 受体介导）不是必需的，后者似乎涉及 Pannexin 膜通道（Pellegrin & Suprenenant 2006）。激活剂直接结合 NLRP3 尚未被证明，激活的确切过程尚不清楚，尽管推测涉及构象变化，从而释放 NACHT 域以进行寡聚化（Inohara & Nunez 2001, 2003）。
英文描述
TRAIL signaling Tumor necrosis factor-related apoptosis-inducing ligand or Apo 2 ligand (TRAIL/Apo2L) is a member of the tumor necrosis factor (TNF) family. This group of apoptosis induction pathways all work through protein interactions mediated by the intracellular death domain (DD), encoded within the cytoplasmic domain of the receptor. TRAIL selectively induces apoptosis through its interaction with the Fas-associated death domain protein (FADD) and caspase-8/10 (Wang S & el-Deiry WS 2003; Sprick MR et al. 2002). TRAIL and its receptors, TRAIL-R1 and TRAIL-R2, were shown to be rapidly endocytosed via clathrin-dependent and -independent manner in human Burkitt's lymphoma B cells (BJAB) (Kohlhaas SL et al. 2007). However, FADD and caspase-8 were able to bind TRAIL-R1/R2 in TRAIL-stimulated BJAB cells at 4oC (at which membrane trafficking is inhibited), suggesting that the endocytosis was not required for an assembly of the functional TRAIL DISC complex. Moreover, blocking of clathrin-dependent endocytosis did not interfere with the capacity of TRAIL to promote apoptosis (Kohlhaas SL et al. 2007).
所含基因
8 个基因