MECHANISMS OF PROGRAMMED CELL DEATH

我们目前正在研究程序化细胞的机制， 通过鉴定凋亡细胞内的稳定结构域 效应器及其目标。 目前有两条道路 CD95/Fas/APO-1通路和TNFR-1通路。 Fas介导的依赖于效应分子的募集， 将受体接收的信号传递给PCD酶 （所谓的半胱天冬酶）。 效应器FADD、RIP、Mort1和RAIDD为 所有这些目前都在研究中，以确定稳定的功能结构域 利用蛋白水解/MALDI质谱的组合， 结合体外和体内功能测定， 识别的碎片。 在确认功能结构域后， 将使用以下组合来确定复杂结构： 多核NMR和/或X射线晶体学。 在相关的途径中， 以TNFR-1为中心的第二种受体系统正在研究中， 既能刺激死亡又能激活 NF-κ B通路。 在这方面，受影响者TRADD和TRAF 蛋白质正在研究中，试图阐明它们的相反方向， 对细胞生命周期的影响。 同样，我们的目标是解构 将系统划分为相关部分，并确定结构 功能性复合物。

We are presently investigating the mechanisms of programmed cell death PCD by identifying stable structural domains within apoptotic effectors and their targets. Two pathways are currently investigated--the CD95/Fas/APO-1 pathyway and the TNFR-1 pathway. Fas-mediated is dependent on the recruitment of effector molecules to transmit the signal received by the receptor to the PCD enzymes (so-called caspases). The effectors FADD, RIP, Mort1 and RAIDD are all presently under study to identify the stable functional domains utilizing a combination of proteolysis/MALDI mass spectrometry in conjuunction with in vitro and in vivo functional assays of the identified pieces. Subsequent to confirmation of functional domains, the complex structures will be determined using a combination of multi-nuclear NMR and/or X-ray crystallography. In a related pathway, a second receptor system centered around TNFR-1 is being investigated, both for its ability to stimulate death as well as to activate the NF-kappaB pathway. In this regard, the effectors TRADD and the TRAF proteins are under study in an effort to elucidate their opposing effects on the cellular life cycle. Again, the goal is to deconstruct the system into the relevant parts and determine th e structures of the functional complexes.