Post-translational Modifications of IκBα: The State of the Art

Abstract

The nuclear factor-kappa B (NF-κB) signaling pathway regulates a variety of biological functions in the body, and its abnormal activation contributes to the pathogenesis of many diseases, such as cardiovascular and respiratory diseases and cancers. Therefore, to ensure physiological homeostasis of body systems, this pathway is strictly regulated by IκBα transcription, IκBα synthesis, and the IκBα-dependent nuclear transport of NF-κB. Particularly, the post-translational modifications of IκBα including phosphorylation, ubiquitination, SUMOylation, glutathionylation and hydroxylation are crucial in the abovementioned regulatory process. Because of the importance of the NF-κB pathway in maintaining body homeostasis, understanding the post-translational modifications of IκBα can not only provide deeper insights into the regulation of NF-κB pathway but also contribute to the development of new drug targets and biomarkers for the diseases.

Elevated NF-κB/SHh/GLI1 Signature Denotes a Worse Prognosis and Represent a Novel Potential Therapeutic Target in Advanced Prostate Cancer

“…To gain more insight about the NF-κB(p65)-SHh-GLI1 axis in PCa, we analyzed both NF-κB(p65) and SHh-GLI1 pathways in Western blot. As shown, IκBα protein, a marker of NF-κB activation [42], was present only in AI cell lines, while no expression was observed in AD cells (Figures 3C and S3A-F). Surprisingly, all three SHh isoforms were expressed in the PC3 cell line, while DU145 and LNCaP did not show the N-terminal active We further evaluated how NF-κB genetic blockade affected SHh signaling in these cell lines.…”

NF-κB inhibitor alpha has a cross-variant role during SARS-CoV-2 infection in ACE2-overexpressing human airway organoids

“…The IκBα protein can be phosphorylated by upstream kinases in a process that destabilizes the inhibitor and facilitates p65 nuclear translocation and transcriptional activity. 32 To determine the role of IκBα in the infectious process, we stably overexpressed an IκBα construct in A549-ACE2 cells with the serine residues at positions 32 and 36 mutated to alanine to prevent phosphorylation. 33 This generates a “super-inhibitor” that is unresponsive to cell signals and is highly active in retaining p65 in the cytoplasm, preventing its transcriptional activity in the nucleus.…”

Ultrasound‐targeted cationic microbubbles combined with the NFκB binding motif increase SDF‐1α gene transfection: A protective role in hearts after myocardial infarction

“…Generally, when cells are stimulated, the NLS polypeptide in the N ‐terminal Rel‐homology domain of NF‐κB is subsequently exposed and recognized by the nuclear transport receptor importin α/β in the cytoplasm. Their binding forms a nuclear complex that is transferred to the nucleus through the NPC in an energy‐dependent manner 27 . In early 1999, it was postulated that the binding of transcription factors to their corresponding sequences in pDNA leads to the nuclear transport of pDNA through the NPC 28 .…”

“…Their binding forms a nuclear complex that is transferred to the nucleus through the NPC in an energydependent manner. 27 In early 1999, it was postulated that the binding of transcription factors to their corresponding sequences in pDNA leads to the nuclear transport of pDNA through the NPC. 28 Here, we inserted a specific DNA targeting sequence (five optimal repeats of the NFκB binding motif) into the pDNA-carrying target gene.…”