《生命科学》 2010, 22(11): 1154-1160
摘 要：摘 要：细胞凋亡是细胞生命活动中一种预定的、并受到严格控制的程序性死亡，它是细胞内一系列促凋亡因子和抗凋亡因子相互作用后获得平衡的结果。细胞凋亡的调控可以发生在表观遗传、转录、翻译、修饰、转运等不同水平，也可以发生在细胞不同的区域，如细胞核、胞质、线粒体、质膜等处。作者近年来发现的新的促/抗凋亡因子从多种不同的角度去诠释细胞凋亡网络的调控。例如，Caspase新的激活机制；凋亡蛋白磷酸化和泛素化修饰以及蛋白通过对中间纤维的影响来诱导线粒体介导的凋亡等等。另外，对凋亡信号如何从胞核流向胞质进而促发线粒体引起的凋亡途径也进行了描述。这些新的凋亡调控机理进一步证明了，细胞凋亡可以发生在细胞生长发育不同的时相和空间，并存在着一个极其复杂的信号传递网络，这一调控网络一旦失去平衡，细胞会引发肿瘤。
关键词：细胞凋亡；p53；天冬氨酸特异性半胱氨酸蛋白酶；泛素连接酶；肿瘤发生；中间纤维
Abstract: Abstract: Apoptosis， or programmed cell death， is a default and well-controlled process during the cell development. It reflects the net balance of interactions among various pro-apoptotic and anti-apoptotic factors. Regulations of apoptosis can occur at the levels of epigenetical regulation， transcription， translation， posttranslational modifications or transport. Also it can take place within different cellular compartments， such as nucleus， cytosol， plasma member and mitochondria. This short review intends to exemplify some new apoptosis mechanisms using newly-defined pro- or anti-apoptotic factors recently characterized in our laboratory. For example， we characterized a novel activating mechanism for caspase-8; we described a specific phosphorylation on E3 ligase Pirh2， which led to the change in its target p53 stability; we also demonstrated how a E3 ligase Pirh2 can act as holder for intermediate filament， thus to stabilize mitochondria， avoiding triggering apoptosis. In addition， the signal transduction pathway that apoptotic signals flow from nucleus to cytosol and finally to mitochondria is also described. All these new findings， together with what had been reported， demonstrate that it truly exists a complicated network for apoptotic signaling within the cell， once it breaks， tumorgenesis begins.
Key words: apoptosis; p53; caspase; E3 ligase; tumorgenesis; intermediate filaments (IFs)
