Inducible transcription factors response

Nuclear factor kappa B (NF-kB) serves as a central regulator of the human immune and inflammatory response, and is a family of inducible transcription factors found virtually ubiquitously in all cells and functions in a variety of human diseases including those related to inflammation, cancer, asthma, atherosclerosis, AIDS, septic shock, and arthritis. Due to its role in a wide variety of diseases, NF-kB has become one of the major targets for drug development. Inhibition of NF-kB activity potentially contributes to cancer chemoprevention [27,28]. 

By virtue of their ability to interact with a repertoire of molecules within the cell, ranging from DNA response elements and protein accessory factors, the NRs represent a target class of complex, multitasking proteins (see Refs. [52, 53] for reviews). Most of the NRs were initially considered to be simple ligand-induced transcription factors. However, studies over the past decade have revealed that NRs are much more complicated and serve more than a unified functional purpose. In this section we will highlight some of the types of activities of NRs using particular examples. 

NF-kB comprises a family of inducible transcription factors that serve as relevant mediators of the inflammatory response. This factor is also involved in protecting cells from undergoing apoptosis in response to DNA damage or treatment with cytokine [89]. Normally, NF-kB is kept inactive by a cytoplasmic inhibitor of kB (IkB) proteins, which are phosphorylated by a cellular kinase complex known as IKK, made up of two kinases, IKK-a and IKK-p. The phosphorylation of IkB by these kinases leads to the degradation of the proteins and to the translocation of NF-kB to the nucleus. Once in the nucleus, NF-kB activates gene expression of cells exposed to growth factors and cytokines [90,91]. Activation of the NF-kB pathway is thus involved in the pathogenesis of chronic inflammatory diseases such as rheumatoid arthritis and asthma... 

Sowter HM, Raval RR, Moore JW, Ratcliffe PJ, Harris AL. Predominant role of hypoxia-inducible transcription factor (Hif)-lalpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia. Cancer Res 2003 63 6130-6134. 

The best characterized response to LPS is the activation of the inducible transcription factor nuclear factor-KB (NF-kB) NF-kB promotes the transcription of many LPS response genes such as the kappa genes in 70Z/3 cells and the interleukins or turmor necrosis factor in macrophages [78]. 

Bruick, R. (2003) Oxygen sensing in the hypoxic response pathway Regulation of the hypoxia-inducible transcription factor. Genes Development, 17,2614-2623. 

Kohler I, Rieber EP. AUergy-associated I epsilon and Ec epsilon receptor II (CD23b) genes activated via binding of an interleukin -induced transcription factor to a novel responsive element. Eur J Immunol 1993 23 3066-3071. 

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