Laboratory of Host Defense Modulation, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea.
Korean J Physiol Pharmacol. 2014 Feb;18(1):73-8. doi: 10.4196/kjpp.2014.18.1.73. Epub 2014 Feb 13.
Cell death and survival are tightly controlled through the highly coordinated activation/inhibition of diverse signal transduction pathways to insure normal development and physiology. Imbalance between cell death and survival often leads to autoimmune diseases and cancer. Death receptors sense extracellular signals to induce caspase-mediated apoptosis. Acting upstream of CED-3 family proteases, such as caspase-3, Bcl-2 prevents apoptosis. Using short hairpin RNAs (shRNAs), we suppressed Bcl-2 expression in Jurkat T cells, and this increased TCR-triggered AICD and enhanced TNFR gene expression. Also, knockdown of Bcl-2 in Jurkat T cells suppressed the gene expression of FLIP, TNF receptor-associated factors 3 (TRAF3) and TRAF4. Furthermore, suppressed Bcl-2 expression increased caspase-3 and diminished nuclear factor kappa B (NF-κB) translocation.
细胞的生与死是通过多种信号转导途径的高度协调的激活/抑制来严格控制的，以确保正常的发育和生理机能。细胞死亡与生存之间的失衡常常导致自身免疫性疾病和癌症。死亡受体感知细胞外信号，诱导半胱天冬酶介导的细胞凋亡。Bcl-2 位于 CED-3 家族蛋白酶（如 caspase-3）的上游，可阻止细胞凋亡。我们使用短发夹 RNA（shRNA）抑制 Jurkat T 细胞中的 Bcl-2 表达，这增加了 TCR 触发的 AICD，并增强了 TNFR 基因的表达。此外，Jurkat T 细胞中 Bcl-2 的敲低抑制了 FLIP、TNF 受体相关因子 3（TRAF3）和 TRAF4 的基因表达。此外，抑制 Bcl-2 的表达增加了 caspase-3 的表达，并减少了核因子 kappa B（NF-κB）的易位。
