Endogenous inhibitors of nuclear factor-kappaB, an opportunity for cancer control.
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.
Chen
Fei
F
The Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA. LFD3@cdc.gov
D019390:Arrestins / Q000502:physiology*; D004268:DNA-Binding Proteins; D000074749:Deubiquitinating Enzyme CYLD; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D009687:Nuclear Proteins; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000502:physiology; D011506:Proteins / Q000502:physiology*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D000071557:beta-Arrestins
D019390:Arrestins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; D000071557:beta-Arrestins; C037112:9-deoxy-delta-9-prostaglandin D2; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D015230:Prostaglandin D2