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Since its first discovery in the early 90’s, the NF-kB/Rel transcription factor family has drawn the attention of experimental biologists, medical profession, and biotech/pharmaceutical industries for its broad and diverse roles in all aspects of human biology and disease. NF-kB/Rel Transcription Factor Family intends to provide an up-to-date guide to the ever-expanding knowledge in the field of NF-kB/Rel transcription factor family.
The mammalian Rel/NF-[kappa]B family of transcription factors plays a central role in the immune system by regulating various processes involving in both innate and adaptive immunity, inflammation, lymphocyte differentiation, and lymphoid malignancies. A wide variety of signals activate NF-[kappa]B driven gene expression through different NF-[kappa]B signaling pathways in a stimulus- and cell type-dependent manner. Due to the diverse regulatory mechanism acting on NF-[kappa]B signaling, the signal dependent activation of NF-[kappa]B remains a challenging area of research. This thesis describes the mechanism of gene regulation by the NF-[kappa]B p52 homodimer with its specific transcriptional co-regulator Bcl3. Chapter I introduces the NF- & kappa;B family transcription factors together with its regulation through the I[kappa]B family, NF-[kappa]B signaling pathways, and its DNA recognition in gene transcription initiation. Chapter II describes the promoter specificity by NF-[kappa]B p52 homodimers. Our results show that a single nucleotide change in the central base pair of [kappa]B DNA discriminates between classical RelA containing NF-[kappa]B dimers versus the p52:Bcl3 complex. Chapter III studies the degradation, re-synthesis, and processing of NF-[kappa]B2/p100 and the generation of p52 in non-canonical NF-[kappa]B signaling pathway as well as inhibitory function of NF-[kappa]2/p100 referred as I[kappa]B[delta]. Our results showed that LT[beta]-mediated non-canonical signaling is a NIK-dependent biphasic event, which induces both the activation and suppression of NF-[kappa]B activity. Chapter IV studies the phosphorylation state of Bcl3 and its function in terms of p52:Bcl3 gene activation. Two new Bcl3 phosphorylation sites were identified and biochemical analysis showed that these two phosphorylations enhance the protein-protein interaction between p52 and Bcl3, which in turn enhance their specific gene activation. Chapter V employed a combination of X-ray crystallography and biochemical technique to investigate the molecular basis of p52:Bcl3 complex formation. Stable p52:Bcl3 core complex was identified and crystallized.
This volume has a strong focus on homo-oligomerization, which is surprisingly common. However, protein function is so often linked to both homo- and hetero-oligomerization and many heterologous interactions likely evolved from homologous interaction, so this volume also covers many aspects of hetero-oligomerization.
Immunity and Inflammation in Health and Disease: Emerging Roles of Nutraceuticals and Functional Foods in Immune Support provides a comprehensive description of the various pathways by which the vertebrate immune system works, the signals that trigger immune response and how fnew and novel nutraceuticals and functional foods, can be used to contain inflammation and also to boost immunity and immune health. Inflammation is a tool to fight pathogens and the vertebrate immune system has a very complex network of cells to achieve this. However inflammation that goes awry is also the leding cause of several diseases ranging from cardiovascular diseases to diabetes. This book covers the entire gamut from the various cellular players in the inflammation-immune response to its ramifications in terms of protection against pathogens as well as in onset of metabolic, aging and auto-immune related diseases. Finally, the balancing role of dietary nutrients between host defence and immune support is also showcased. The first three scetions explain the various components of the immune system and their modes of activation. The fourth section deals with the ramifications of a robust and execessive inflammatory response. The fifth section is focused on the association between nutrition and immunity and how deficiencies in certain nutrients may affect immunocompetence. The sixth section chapters represent a vision of paradigm shifts within the field and discusses possible future directions. This bool will be a valuable reference for researchers studying immune health either in academia, or in the nutraceutical or functional food industries. Product developers in nutraceutical, supplement, functional food, and health food companies will also appreciate the information presented here. - Conceptualizes the key features in natural products which can boost immune function and immune health - Explains the intricate mechanistic aspects and balance behind immune health - Presents the pathophysiology of several diseases associated with immune system disruption
Recent evidence proving the molecular link between unchecked, chronic inflammation and cancer has implicated the transcription factor NF-kB as a key factor in both inhibiting apoptosis and promoting cell proliferation. Since its initial identification 20 years ago as a simple regulating factor in one small part of the immune response, NF-kB is proving to be the most protean of all transcription factors. It has been shown to function in most cell types as a key regulator of a number of inducible genes. Research on the responsibilities and resulting pathologies of NF-kB has been prolific, but until now there has been no consolidated, multidisciplinary reference. Providing contributions from leading authorities involved with seminal discoveries on the subject, Handbook of Transcription Factor NF-kappaB is an entry point to understanding the broad role of this widely studied factor. Beginning with a summary, the authors introduce the uninitiated reader to the complexities of the NF-kB system. They explain how a multitude of extracellular and intercellular signals integrated at the level of this transcription factor have led to fundamental insights about many aspects of gene regulation and signal transduction. The chapters delve into specific research aspects concerning the function and regulation of NF-kB in a number of biological systems. They discuss inflammation, innate and adaptive immunity, liver integrity, and nervous system development, as well as the formation of hair, skin, teeth, and many other aspects of the developing vertebrate body. The pathological effects of excess NF-kB activity are addressed in chapters on diseases related to chronic inflammation, such as heart disease, muscular dystrophy, cancer, and tumor proliferation, as well as diseases caused by inherent deficiencies in NF-kB. The text culminates in a discussion of current efforts to develop therapies aimed at inhibiting the aberrant activity of NF-kB in different diseases.
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