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Nuclear Factor Kappa-B: Bridging Inflammation and Cancer
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Mohammad Aslam Khan, Girijesh Kumar Patel, Haseeb Zubair, Nikhil Tyagi, Shafquat Azim, Seema Singh, Aamir Ahmad, Ajay Pratap Singh
NF-κB transcriptionally regulates expression of genes which are involved in cell survival, apoptosis, differentiation and immune responses [42, 43]. As discussed above, NF-κB family consists of five members. Both the precursors (NF-κB1/p105 and NF-κB2/ p100) contain IκB-homologous regions at the C-terminal that function as NF-κB inhibitors. Proteolytic processing removes inhibitory domains, allowing the processed proteins (NF-κB1/ p50 and NF-κB2/p52) to enter into the nucleus. Inside the nucleus, p50 and p52 form homodimers or heterodimers with Rel family proteins [42]. All these NF-κB associated proteins have Rel homology domain (RHD) at the N-terminal region. Some of the NF-κB proteins (p65, c-Rel and RelB) contain transcriptional activation domain (TAD) at C-terminal, and these TAD containing proteins positively regulate transcriptional activity. On the other hand, two TAD lacking proteins, p52 and p100, negatively regulate gene expression when bound as homodimer, but can activate gene expression when recruited with other TAD containing proteins like p65. RelB and cRel [44]. Activation of NF-κB pathway is either by classical/canonical or the alternate/non-canonical signaling pathways.
Effect of inflammation on cytochrome P450-mediated arachidonic acid metabolism and the consequences on cardiac hypertrophy
Published in Drug Metabolism Reviews, 2023
Mohammed A. W. ElKhatib, Fadumo Ahmed Isse, Ayman O. S. El-Kadi
Inactive NF-κB resides in the cytoplasm of every cell as a heterogenous group of hetero- or homodimeric transcription factors comprising different subunits (Aggarwal 2004). These subunits belong to the reticuloendotheliosis (Rel) protein family. The whole five Rel proteins possess the Rel homology domain (RHD) comprising nearly three hundred amino acids which is involved in DNA binding, dimerization, and interacting with NF-κB inhibitor (IκB). These five proteins are NF-κB1 (comprising p50 with its precursor p105), NF-κB2 (comprising p52 with its precursor p100), Rel A (p65), Rel B, and c-Rel. Commonly, the first two proteins are generated as large precursors (p100 and p105) which are further transformed into smaller proteins with transcriptional activity, while the latter three are produced as active transcriptional factors (May and Ghosh 1998; McKay and Cidlowski 1999; Bottex-Gauthier et al. 2002; Aggarwal 2004; Sethi et al. 2008; Prasad et al. 2010).
PU.1 interaction with p50 promotes microglial-mediated inflammation in secondary spinal cord injury in SCI rats
Published in International Journal of Neuroscience, 2023
Mingchen Yu, Yiqing Ou, Hongmei Wang, Weidong Gu
NF-κB is a classical signal pathway of inflammation and important molecular mechanism of microglia hyperactivity in mediating inflammatory reactions and participates in secondary SCI [23,24]. Therefore, we hypothesized that PU.1 is involved in the NF-κB signaling pathway-mediated inflammatory response after SCI. p65/p50 is known as the main execution factor of the NF-κB signal pathway, which form dimers of homologous structures [25,26]. p50 is a DNA-binding site, and p65 enhances transcriptional activity through the synergistic effect on the Rel homology domain of p50, and promotes p50 and DNA binding [27,28]. Although p50 alone cannot activate transcription, p65 entry into the nucleus depends on p50, and p65 can only cause activation when p50 binds to a specific DNA target sequence [27,29].
How do nuclear factor kappa B (NF-κB)1 and NF-κB2 defects lead to the incidence of clinical and immunological manifestations of inborn errors of immunity?
Published in Expert Review of Clinical Immunology, 2023
Nazanin Fathi, Hanieh Mojtahedi, Marzieh Nasiri, Hassan Abolhassani, Mahsa Yousefpour Marzbali, Marzie Esmaeili, Fereshte Salami, Furozan Biglari, Nima Rezaei
NF-κB family are the ubiquitous transcription factors, which contain five members: NF-κB1 (p105-p50), NF-κB2 (p100-p52), RelA (p65), RelB, and c-Rel. These factors collaborate to form hetero or homo dimers, which regulate the expression of several genes that are essential for many cellular processes. Structurally, NF-κBs have a conserved amino terminus (N) and a Rel homology domain (RHD), where sequences are required for dimerization, DNA binding, and nuclear localization. The cleaved forms of NF-κB1 (P50) and NF-κB2 (P52), which only comprise the RHD, serve as an active transcription factor [10] (Figure 1). Generally, NF-κB proteins are trapped in the cytoplasm by inhibitors of NF-κB proteins (IκBs), such as IκBα, IκBκ, and IκBɛ and prevent the nuclear entry of these transcription factors.