英-核因子KB的上有信号传到.doc

Upstream Signal Transduction of NF-kB Activation Fei Chen§, Jacquelyn Bower, Laurence M. Demers?, and Xianglin Shi The Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA; ?Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA § To whom correspondence should be addressed at: Dr. Fei Chen PPRB/NIOSH, 1095 Willowdale Road, Morgantown, WV 26505 Tel: (304) 285-6021, Fax: (304) 285-5938, E-mail: lfd3@cdc.gov December 2001 ? ? ? Abstract NF-?B is a transcription factor governing the expression of genes involved in the immune response, embryo or cell lineage development, cell apoptosis, cell cycle progression, inflammation, and oncogenesis. During past few years, tremendous attention has been focused on the upstream signaling pathways leading to the activation of this transcription factor. Many of these signaling molecules can serve as potential pharmaceutical targets for the specific inhibition of NF-?B activation and the subsequent interference of disease processes. However, how these molecules interact with each other is still a debatable issue. Since many nodal signal molecules in this pathway relay more than one of the upstream signals to their downstream targets, it has been speculated that the transmission of signals involves a network, rather than a linear sequence in the activation of NF-?B. Thus, elucidation of the detailed relationships among the upstream signaling molecules of NF-?B activation will be important in developing pharmaceutical inhibitors that specifically inhibit the activation of NF-?B. Such inhibitors would be predicted to have powerful anti-inflammatory and/or anti- carcinogenic effects. ? Key words: IKK, kinases, NF-?B, ROIs, signal transduction, ubiquitination. The NF-?B transcription factor was first discovered in 1986 . Knowledge of the activation of this transcription factor lagged behind the unde