NFKBIA

Case study 1: Yanquan Li, 2023

The nuclear factor-κB (NF-κB) signaling pathway regulates specific immunological responses and controls a wide range of physiological processes. NF-κB inhibitor alpha (IKBA) is an NF-κB inhibitory mediator in the cytoplasm that modulates the nuclear translocation and DNA binding activities of NF-κB proteins. However, whether the upstream cascade of the canonical NF-κB signaling pathway has physiological roles independent of IKBA-mediated transcriptional activation remains unclear. Herein the researchers investigated the function of IKBA in mature sperm in which transcriptional and translational events do not occur. IKBA was highly expressed in human sperm. The repression of IKBA phosphorylation by its inhibitor Bay117082 markedly enhanced sperm motility. On the contrary, lipopolysaccharide-stimulated IKBA phosphorylation significantly decreased sperm motility. Nevertheless, Bay117082 treatment did not affect the motility of IKBA-knockout sperm. Further, untargeted metabolomic analysis and pharmacological blocking assays revealed that the Bay117082-induced increase in sperm motility was attributable to fatty acid β-oxidation (FAO) enhancement.

Fig1. Phosphorylation states of IKKA/B, RELA and IKBA proteins in human sperm in PBS and BWW media. α-Tubulin served as the loading control.

Fig2. Distribution of IKBA in sperm of control mice and Nfkbia cKO mice. DAPI (blue) labeled the nuclei, and IKBA was stained with Alexa Fluor 488 (green).

Case study 2: Holly E Dembinski, 2017

Stress-response transcription factors such as NFκB turn on hundreds of genes and must have a mechanism for rapid cessation of transcriptional activation. The researchers recently showed that the inhibitor of NFκB signaling, IκBα, dramatically accelerates the dissociation of NFκB from transcription sites, a process they have called "stripping." To test the role of the IκBα C-terminal PEST (rich in proline, glutamic acid, serine, and threonine residues) sequence in NFκB stripping, a mutant IκBα was generated in which five acidic PEST residues were mutated to their neutral analogs. This IκBα(5xPEST) mutant was impaired in stripping NFκB from DNA and formed a more stable intermediate ternary complex than that formed from IκBα(WT) because DNA dissociated more slowly. NMR and amide hydrogen-deuterium exchange mass spectrometry showed that the IκBα(5xPEST) appears to be "caught in the act of stripping" because it is not yet completely in the folded and NFκB-bound state. When the mutant was introduced into cells, the rate of postinduction IκBα-mediated export of NFκB from the nucleus decreased markedly.

Fig3. Rates of IκBα PEST mutants associating with NFκB by stopped-flow fluorescence following the native IκBα Trp258.

Fig4. After a pulse of TNFα, the same cells showed a markedly diminished rate of export of GFP–NFκB from the nucleus when IκBα(5xPEST) replaced IκBα(WT).

Fig1. Diagram depicting the regulation mechanism of IKBA phosphorylation in sperm motility. (Yanquan Li, 2023)

Fig2. Schematic outlining stimulus-induced activation of NF-κB. (Stephanie M E Truhlar, 2008)

NFKBIA involved in several pathways and played different roles in them. We selected most pathways NFKBIA participated on our site, such as cAMP signaling pathway, Chemokine signaling pathway, NF-kappa B signaling pathway, which may be useful for your reference. Also, other proteins which involved in the same pathway with NFKBIA were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

NFKBIA has several biochemical functions, for example, NF-kappaB binding, enzyme binding, heat shock protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by NFKBIA itself. We selected most functions NFKBIA had, and list some proteins which have the same functions with NFKBIA. You can find most of the proteins on our site.

NFKBIA has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with NFKBIA here. Most of them are supplied by our site. Hope this information will be useful for your research of NFKBIA.

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