title: Regulation of IkappaBalpha function and NF-kappaB signaling: AEBP1 is a novel proinflammatory mediator in macrophages.
abstract: NF-kappaB comprises a family of transcription factors that are critically involved in various inflammatory processes. In this paper, the role of NF-kappaB in inflammation and atherosclerosis and the regulation of the NF-kappaB signaling pathway are summarized. The structure, function, and regulation of the NF-kappaB inhibitors, IkappaBalpha and IkappaBbeta, are reviewed. The regulation of NF-kappaB activity by glucocorticoid receptor (GR) signaling and IkappaBalpha sumoylation is also discussed. This paper focuses on the recently reported regulatory function that adipocyte enhancer-binding protein 1 (AEBP1) exerts on NF-kappaB transcriptional activity in macrophages, in which AEBP1 manifests itself as a potent modulator of NF-kappaB via physical interaction with IkappaBalpha and a critical mediator of inflammation. Finally, we summarize the regulatory roles that recently identified IkappaBalpha-interacting proteins play in NF-kappaB signaling. Based on its proinflammatory roles in macrophages, AEBP1 is anticipated to serve as a therapeutic target towards the treatment of various inflammatory conditions and disorders.
authors.affiliation: Department of Biology and Chemistry, Faculty of Arts and Sciences, American University of Sharjah, P.O. Box 26666, Sharjah, UAE. amajdalawieh@aus.edu
authors.forename: Amin
authors.initials: A
authors.lastname: Majdalawieh
authors.forename: Hyo-Sung
authors.initials: HS
authors.lastname: Ro
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism; D002268:Carboxypeptidases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D000071518:Liver X Receptors; D008264:Macrophages / Q000276:immunology / Q000502:physiology*; D008969:Molecular Sequence Data; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D012772:Shock, Septic / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C484818:AEBP1 protein, human; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D000071518:Liver X Receptors; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D011965:Receptors, Glucocorticoid; D012097:Repressor Proteins; D000072000:NF-KappaB Inhibitor alpha; D002268:Carboxypeptidases
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