TNFSF10(肿瘤坏死因子超家族成员10,TNF superfamily member 10),也称为TRAIL(TNF-related apoptosis-inducing ligand,肿瘤坏死因子相关凋亡诱导配体),是一种重要的细胞因子,属于肿瘤坏死因子超家族(TNF superfamily)。该基因家族成员通常以跨膜蛋白形式存在,通过结合特定受体调控免疫反应、细胞凋亡和炎症等过程。TNFSF10的主要功能是诱导程序性细胞死亡(凋亡),尤其在癌细胞中发挥选择性杀伤作用,而对正常细胞影响较小。其作用位点是通过与死亡受体DR4(TRAIL-R1)和DR5(TRAIL-R2)结合,激活下游 caspase 级联反应(一组促进细胞凋亡的蛋白酶),最终导致细胞凋亡。TNFSF10的突变可能削弱其诱导凋亡的能力,与肿瘤免疫逃逸相关,例如某些癌症中受体DR4/DR5的突变会降低TNFSF10的敏感性。该基因过表达可能增强抗肿瘤效应,但过度激活也可能引发正常组织损伤;而表达降低则可能导致免疫监视功能下降,促进肿瘤发展。TNFSF10与多种疾病相关,包括癌症(如结直肠癌、肺癌)、自身免疫性疾病和病毒感染(如HIV)。在基因家族共性方面,TNF超家族成员均含有一段保守的“TNF同源结构域”,通常以三聚体形式发挥作用,通过结合TNFR超家族受体调控细胞存活、分化或死亡。目前针对TNFSF10的疗法(如重组TRAIL或DR4/DR5激动剂)正在癌症治疗中开展研究。
The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein preferentially induces apoptosis in transformed and tumor cells, but does not appear to kill normal cells although it is expressed at a significant level in most normal tissues. This protein binds to several members of TNF receptor superfamily including TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and possibly also to TNFRSF11B/OPG. The activity of this protein may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and TNFRSF11B/OPG that cannot induce apoptosis. The binding of this protein to its receptors has been shown to trigger the activation of MAPK8/JNK, caspase 8, and caspase 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]
由该基因编码的蛋白是属于肿瘤坏死因子(TNF)配体家族的细胞因子。该蛋白质优选诱导细胞凋亡的转化和肿瘤细胞,但不会出现虽然它是在大多数正常组织一个显著水平表达杀死正常细胞。这种蛋白质结合TNF受体超家族包括TNFRSF10A / TRAILR1,TNFRSF10B / TRAILR2,TNFRSF10C / TRAILR3,TNFRSF10D / TRAILR4,也可能为TNFRSF11B / OPG的几名成员。该蛋白质的活性可以通过结合到诱饵受体TNFRSF10C / TRAILR3,TNFRSF10D / TRAILR4和TNFRSF11B / OPG不能诱导细胞凋亡进行调制。该蛋白质与其受体的结合已被证明触发MAPK8 / JNK,胱天蛋白酶8活化,和caspase 3.或者剪接转录变体编码不同同种型已发现此基因。 [由RefSeq的,2010年7月提供]
TNFSF10基因(以及对应的蛋白质)的细胞分布位置:
TNFSF10基因的本体(GO)信息:
名称 |
---|
4068 FoxO signaling pathway [PATH:hsa04068] |
4060 Cytokine-cytokine receptor interaction [PATH:hsa04060] |
4210 Apoptosis [PATH:hsa04210] |
4650 Natural killer cell mediated cytotoxicity [PATH:hsa04650] |
5162 Measles [PATH:hsa05162] |
5164 Influenza A [PATH:hsa05164] |
名称 |
---|
Apoptosis |
CASP8 activity is inhibited |
Caspase activation via extrinsic apoptotic signalig pathway |
Death Receptor Signalling |
Dimerization of procaspase-8 |
Ligand-dependent caspase activation |
Programmed Cell Death |
Regulated Necrosis |
Regulation by c-FLIP |
Regulation of necroptotic cell death |
RIPK1-mediated regulated necrosis |
TRAIL signaling |
疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
Liver carcinoma | 0.149646753 | 52 | 0 | BeFree_CTD_human_LHGDN |
Glioma | 0.142860706 | 31 | 0 | BeFree_CTD_human_LHGDN |
Mammary Neoplasms | 0.140699103 | 14 | 1 | BeFree_CTD_human_LHGDN |
Neuroblastoma | 0.132244679 | 18 | 0 | BeFree_CTD_human_LHGDN |
Prostatic Neoplasms | 0.129258818 | 11 | 0 | BeFree_CTD_human_LHGDN |
leukemia | 0.127610304 | 19 | 0 | BeFree_CTD_human_LHGDN |
Liver neoplasms | 0.12434307 | 17 | 0 | BeFree_CTD_human |
Colonic Neoplasms | 0.123538676 | 5 | 0 | BeFree_CTD_human_LHGDN |
Neoplasm Metastasis | 0.123528744 | 14 | 0 | BeFree_CTD_human |
Influenza | 0.123267234 | 4 | 0 | BeFree_CTD_human_LHGDN |
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