COBRE PROJ 6: PROGRAMMED DEATH PATHWAY INITIATED FROM THE ENDOPLASMIC RETICULUM

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 Chi Li，PI，项目6 这项建议的目的没有改变。它们旨在研究调节内质网（ER）启动的程序性细胞死亡的分子机制。 程序性细胞死亡在癌症的发生发展中起着重要的作用，而癌症的标志之一就是程序性细胞死亡的抑制。 在各种死亡信号下，细胞可以从不同的亚细胞区室启动死亡途径。 虽然很多注意力都集中在线粒体启动的死亡途径，相对较少的是知道的程序性细胞死亡过程中的ER的参与。 目前尚不清楚来自ER应激的信号如何转导以诱导细胞死亡。 为解决这一问题，设想了三个具体目标： 1.研究内质网应激诱导细胞死亡过程中内质网腔释放死亡诱导因子的机制。 2.研究来自ER的死亡诱导因子激活的信号通路。 3.确定ER特异性死亡途径如何与线粒体起始的死亡途径进行通信。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chi Li, PI, Project 6 The aims of this proposal have not changed. They are designed to examine the molecular mechanisms that regulate programmed cell death initiated from the endoplasmic reticulum (ER). Programmed cell death plays an important role in cancer development, and one of the hallmarks of cancer is the inhibition of programmed cell death. Upon a variety of death signals, cells can initiate death pathways from different subcellular compartments. Although much attention has been focused on the death pathway initiated from mitochondria, relatively little is known about the involvement of the ER during programmed cell death. It remains unclear how signals from ER stress are transduced to induce cell death. To address this question, three specific aims are envisioned: 1. Study the mechanisms of releasing death-inducing factors from the ER lumen during ER stress-induced cell death. 2. Investigate the signaling pathway activated by death-inducing factors from the ER. 3. Determine how the ER-specific death pathway communicates with the death pathway initiated from mitochondria.