Dudekula Subhan, Lee Ming-Hui, Hsu Li-Jin, Chen Shean-Jen, Chang Nan-Shan
Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
Aging (Albany NY). 2010 Dec;2(12):1023-9. doi: 10.18632/aging.100263.
Zfra (zinc finger-like protein that regulates apoptosis) is a naturally occurring short peptide consisting of 31 amino acids, which regulates tumor necrosis factor (TNF)-mediated cell death by interacting with receptor adaptor protein TRADD (TNF receptorassociated death domain protein) and downstream JNK (c-Jun N-terminal kinase), NF-κB (Nuclear factor kappa B) and WWOX/WOX1 (WW domain-containing oxidoreductase). Cytochrome c release is generally considered as a pivotal step in apoptosis. Remarkably, overexpressed Zfra induces apoptosis via the mitochondrial pathway, which involves suppression of Bcl-2 and Bcl-xL expression (without causing cytochrome c release), counteracting the apoptotic function of tumor suppressor p53 and WWOX, and dissipation of mitochondrial membrane potential for ultimately leading to cell death. Control of cellular aging and apoptosis by Zfra, p53 and WWOX is discussed.
Zfra（调节细胞凋亡的锌指样蛋白）是一种天然存在的由31个氨基酸组成的短肽，它通过与受体衔接蛋白TRADD（肿瘤坏死因子受体相关死亡结构域蛋白）以及下游的JNK（c-Jun氨基末端激酶）、NF-κB（核因子κB）和WWOX/WOX1（含WW结构域的氧化还原酶）相互作用来调节肿瘤坏死因子（TNF）介导的细胞死亡。细胞色素c的释放通常被认为是细胞凋亡中的关键步骤。值得注意的是，过表达的Zfra通过线粒体途径诱导细胞凋亡，这涉及抑制Bcl-2和Bcl-xL的表达（不引起细胞色素c的释放），抵消肿瘤抑制因子p53和WWOX的凋亡功能，以及线粒体膜电位的耗散，最终导致细胞死亡。文中讨论了Zfra、p53和WWOX对细胞衰老和凋亡的调控。
