Chen Fei
The Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA.
Cancer Res. 2004 Nov 15;64(22):8135-8. doi: 10.1158/0008-5472.CAN-04-2096.
Excessive and prolonged activation of nuclear factor-kappaB (NF-kappaB) has been linked to numerous human diseases, especially cancer, because of the elevated expression of genes encoding antiapoptotic proteins, cytokines, chemokines, cell adhesion molecules, and so on. Eukaryotic cells have developed multiple mechanisms to keep this ubiquitous transcription factor in check. In addition to the inhibitor of kappaB family proteins, a number of endogenous molecules that negatively regulate the activation or activity of NF-kappaB have been identified. These molecules include A20, CYLD, cyPG15-deoxy-Delta(12,14)-prostaglandin J(2), Foxj1, Twist proteins, and beta-arrestins. The extended list of these endogenous inhibitors of NF-kappaB may provide new opportunities for the development of novel strategies for the intervention of malignant transformation. The question to be asked is how NF-kappaB is sustained activated in a number of cancers in which so many antagonists are surrounded.
核因子-κB（NF-κB）的过度和长期激活与多种人类疾病相关，尤其是癌症，这是因为编码抗凋亡蛋白、细胞因子、趋化因子、细胞黏附分子等的基因表达升高。真核细胞已发展出多种机制来控制这种普遍存在的转录因子。除了κB抑制蛋白家族外，还鉴定出了许多负向调节NF-κB激活或活性的内源性分子。这些分子包括A20、CYLD、环戊前列腺素15-脱氧-Δ（12,14）-前列腺素J2、Foxj1、Twist蛋白和β-抑制蛋白。这些NF-κB内源性抑制剂的不断增加的列表可能为开发干预恶性转化的新策略提供新机会。要问的问题是，在众多拮抗剂环绕的情况下，NF-κB在许多癌症中是如何持续激活的。
