凋亡信号调节激酶1对细胞凋亡的调节作用  

Regulatory Effects of Apoptosis Signal-Regulating Kinase 1 on Apoptosis

作　　者：崔秀云[1] 王红[1] 赵宝昌[1] 

机构地区：[1]大连医科大学,大连116027

出　　处：《中国生物工程杂志》2002年第4期22-28,共7页China Biotechnology

摘　　要：细胞存活与凋亡之间的平衡是多细胞生物正常发育与稳态的关键。细胞凋亡是受多种因素高度调控的细胞程序性死亡过程。凋亡信号调节激酶 1 (ASK1 )是促分裂原活化蛋白激酶激酶激酶家族的成员之一 ,它分别激活SER1 JNK和MKK3 MKK6 p38途径 ,在细胞因子及应激诱导细胞凋亡过程中起着关键作用。TNF受体和Fas信号转导系统在抗凋亡与促凋亡过程中发挥重要作用 ,其中包括TNF受体Ⅰ相关死亡域蛋白 (TRADD)、Fas相关死亡域蛋白 (FADD)等多种蛋白因子。细胞色素C是线粒体依赖性死亡信号 ,受Bcl 2家族蛋白的调节。反应性氧化合物的氧化激活使硫氧还蛋白 (Trx)氧化 ,并与ASK1分离 ,从而激活ASK1造成细胞凋亡。总之 ,许多促凋亡与抗凋亡因子组成复杂的、相互拮抗的机制。在信号转导的各种不同的关卡上 ,这些因子的平衡作用最终决定细胞的生与死。The balance between cell survival and apoptosis is crucial for normal development and homeostasis of multicellular organisms.Apoptosis is a highly regulated and organized death process by various factors.Apoptosis signal\|regulating kinase 1(ASK1) is one member of the mitogen\|activated protein(MAP) kinase kinase kinase family and activates both the SER1\|JNK and MKK3/MKK6\|p38 signaling cascades,plays a critical role in signal transduction of cytokines\| and stress\|induced apoptosis.TNF receptor and Fas signaling play significant role in mediating pro and anti\|apoptotic cellular events,including TNF receptor Ⅰ associated death domain protein(TRADD),Fas\|associated death domain\|containing protein(FADD),and many protein factors.Cytochrome C is mitochondrial dependent death signals and is regulated by Bcl\|2 family proteins.Reactive oxygen species induce oxidative stress,which oxidizes thioredoxin(Trx).The oxidation of Trx results in the dissociation of ASK1 form the ASK1\|Trx complex,and ASK1 is activated and apoptosis is induced.Thus,the complicated and antagonistic machineries are composed of many pro\| and anti\|apoptosis factors.The balancing effects of these factors at various checkpoints of signal transduction culminate in a final decision to die or to live.\;

关 键 词：凋亡信号 调节激酶1 细胞凋亡 调节作用 死亡受体 MAP激酶 线粒体 

分 类 号：Q255[生物学—细胞生物学] Q26