Nuclear transcription factor (NF-κB)

The nuclear transcription factor NF-κB (NF-κB) is a key nuclear transcription factor, usually present in the cytoplasm of almost all types of cells in a non-active form of homologous or heterodimeric. Has very important features. It is involved in the activation of immune cells, the development of T and B lymphocytes, stress response, and apoptosis. Many factors activate the nuclear transcription factor NF-κB, which is transferred from the cytoplasm to the nucleus, binds to the κB site of the NF-κB-responsive gene and regulates the transcription of NF-κB-responsive genes. The nuclear transcription factor NF-κB was originally found in B lymphocytes, which binds to the B site of the immunoglobulin kappa light chain gene enhancer and regulates the transcription of the immunoglobulin kappa light chain, hence the name nuclear transcription factor kappa B. Nuclear transcription factor NF-κB family members usually form complexes with their inhibitory protein IκBs in the form of homodimers or heterodimers, and exist in the cytoplasm in an inactive form, only under the influence of various activation factors, NF -κB can be activated. There are many factors that can activate the nuclear transcription factor NF-κB, including various stress stimuli, bacterial mucopolysaccharides, viruses, oxygen free radicals and various cytokines, which have different mechanisms for activating the nuclear transcription factor NF-κB. With the rapid development of molecular biology in recent years, the activation mechanism of the nuclear transcription factor NF-κB is gradually being clarified. The subunits of NF-κB, p50, p65, p52, c-Rel, and RelB, polymerize to form homologous or heterodimers. Unlike other DNA binding proteins, the NF-κB subunit forms two Ig-like domains in its Rel homology domain (RHD). The main role of the carboxy-terminal end of NF-κB is to polymerize two subunits. The main role of the amino terminus is to form a sequence-specific pocket-like structure that specifically binds to the target gene kappa B site. The ky (ankyrin repeat domain) of the inhibitor IκBs forms a slightly curved cylindrical structure containing an amino acid residue capable of specifically recognizing NF-κB, thereby binding to the Ig-like domain of the polymerized p50/p65. There are 6 kinds of IκBs, which are IκBα, -β, -γ, -ε, -δ, bcl-3. When IκBs binds to the p65 subunit, the spatial conformation of p65 is altered, and the amino terminus of the p65 subunit Ig-like domain is rotated by 180°, thereby concealing key amino acid residues that bind to the target DNA, thus inhibiting NF- Specific binding of kappa B to the regulatory region of the target DNA. The serine residues at positions 32 and 36 of the amino terminus of IκBα and the serine at positions 19 and 23 of IκBβ were phosphorylated by IκB protein kinase (IKKα-IKKβ), and the phosphorylated IκBs were ubiquitinated and further degraded by protease to make NF. -κB is dissociated from the NF-κB-IκBs complex and transferred to the nucleus to bind to the corresponding target gene. However, at the same time, IκBs re-synthesized rapidly after being degraded, and could enter the nucleus to bind to NF-κB, and the formation of NF-κB-IκBs complex detached NF-κB from its binding DNA κB site and re-established Transduction in the cytoplasm, thereby achieving the cycle of activation and inactivation of NF-κB, and completing the function of NF-κB as a nuclear transcription factor to regulate gene transcription. The transcription of more than 60 genes requires the involvement of the nuclear transcription factor NF-κB, such as genes associated with cell adhesion, immune stimulation, apoptosis, inflammatory cell chemotaxis, cell differentiation, and degradation of extracellular matrix. The molecular basis of these important physiological activities is the continuous cycle of activation and inactivation of NF-κB.