2.50
Hdl Handle:
http://hdl.handle.net/10033/288580
Title:
Atypical IκB proteins - nuclear modulators of NF-κB signaling.
Authors:
Schuster, Marc; Annemann, Michaela; Plaza-Sirvent, Carlos; Schmitz, Ingo
Abstract:
Nuclear factor κB (NF-κB) controls a multitude of physiological processes such as cell differentiation, cytokine expression, survival and proliferation. Since NF-κB governs embryogenesis, tissue homeostasis and the functions of innate and adaptive immune cells it represents one of the most important and versatile signaling networks known. Its activity is regulated via the inhibitors of NF-κB signaling, the IκB proteins. Classical IκBs, like the prototypical protein IκBα, sequester NF-κB transcription factors in the cytoplasm by masking of their nuclear localization signals (NLS). Thus, binding of NF-κB to the DNA is inhibited. The accessibility of the NLS is controlled via the degradation of IκBα. Phosphorylation of the conserved serine residues 32 and 36 leads to polyubiquitination and subsequent proteasomal degradation. This process marks the central event of canonical NF-κB activation. Once their NLS is accessible, NF-κB transcription factors translocate into the nucleus, bind to the DNA and regulate the transcription of their respective target genes. Several studies described a distinct group of atypical IκB proteins, referred to as the BCL-3 subfamily. Those atypical IκBs show entirely different sub-cellular localizations, activation kinetics and an unexpected functional diversity. First of all, their interaction with NF-κB transcription factors takes place in the nucleus in contrast to classical IκBs, whose binding to NF-κB predominantly occurs in the cytoplasm. Secondly, atypical IκBs are strongly induced after NF-κB activation, for example by LPS and IL-1β stimulation or triggering of B cell and T cell antigen receptors, but are not degraded in the first place like their conventional relatives. Finally, the interaction of atypical IκBs with DNA-associated NF-κB transcription factors can further enhance or diminish their transcriptional activity. Thus, they do not exclusively act as inhibitors of NF-κB activity. The capacity to modulate NF-κB transcription either positively or negatively, represents their most important and unique mechanistic difference to classical IκBs. Several reports revealed the importance of atypical IκB proteins for immune homeostasis and the severe consequences following their loss of function. This review summarizes insights into the physiological processes regulated by this protein class and the relevance of atypical IκB functioning.
Affiliation:
Systems-oriented Immunology and Inflammation Research, Helmholtz Center for Infection Research, Braunschweig, 38124, Germany. ingo.schmitz@helmholtz-hzi.de.
Citation:
Atypical IκB proteins - nuclear modulators of NF-κB signaling. 2013, 11 (1):23 Cell Commun. Signal
Journal:
Cell communication and signaling : CCS
Issue Date:
2013
URI:
http://hdl.handle.net/10033/288580
DOI:
10.1186/1478-811X-11-23
PubMed ID:
23578005
Type:
Article
Language:
en
ISSN:
1478-811X
Appears in Collections:
publications of the AG system-oriented immunologyand infection research (SIME)

Full metadata record

DC FieldValue Language
dc.contributor.authorSchuster, Marcen_GB
dc.contributor.authorAnnemann, Michaelaen_GB
dc.contributor.authorPlaza-Sirvent, Carlosen_GB
dc.contributor.authorSchmitz, Ingoen_GB
dc.date.accessioned2013-05-07T09:46:44Zen
dc.date.available2013-05-07T09:46:44Zen
dc.date.issued2013en
dc.identifier.citationAtypical IκB proteins - nuclear modulators of NF-κB signaling. 2013, 11 (1):23 Cell Commun. Signalen_GB
dc.identifier.issn1478-811Xen
dc.identifier.pmid23578005en
dc.identifier.doi10.1186/1478-811X-11-23en
dc.identifier.urihttp://hdl.handle.net/10033/288580en
dc.description.abstractNuclear factor κB (NF-κB) controls a multitude of physiological processes such as cell differentiation, cytokine expression, survival and proliferation. Since NF-κB governs embryogenesis, tissue homeostasis and the functions of innate and adaptive immune cells it represents one of the most important and versatile signaling networks known. Its activity is regulated via the inhibitors of NF-κB signaling, the IκB proteins. Classical IκBs, like the prototypical protein IκBα, sequester NF-κB transcription factors in the cytoplasm by masking of their nuclear localization signals (NLS). Thus, binding of NF-κB to the DNA is inhibited. The accessibility of the NLS is controlled via the degradation of IκBα. Phosphorylation of the conserved serine residues 32 and 36 leads to polyubiquitination and subsequent proteasomal degradation. This process marks the central event of canonical NF-κB activation. Once their NLS is accessible, NF-κB transcription factors translocate into the nucleus, bind to the DNA and regulate the transcription of their respective target genes. Several studies described a distinct group of atypical IκB proteins, referred to as the BCL-3 subfamily. Those atypical IκBs show entirely different sub-cellular localizations, activation kinetics and an unexpected functional diversity. First of all, their interaction with NF-κB transcription factors takes place in the nucleus in contrast to classical IκBs, whose binding to NF-κB predominantly occurs in the cytoplasm. Secondly, atypical IκBs are strongly induced after NF-κB activation, for example by LPS and IL-1β stimulation or triggering of B cell and T cell antigen receptors, but are not degraded in the first place like their conventional relatives. Finally, the interaction of atypical IκBs with DNA-associated NF-κB transcription factors can further enhance or diminish their transcriptional activity. Thus, they do not exclusively act as inhibitors of NF-κB activity. The capacity to modulate NF-κB transcription either positively or negatively, represents their most important and unique mechanistic difference to classical IκBs. Several reports revealed the importance of atypical IκB proteins for immune homeostasis and the severe consequences following their loss of function. This review summarizes insights into the physiological processes regulated by this protein class and the relevance of atypical IκB functioning.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Cell communication and signaling : CCSen_GB
dc.titleAtypical IκB proteins - nuclear modulators of NF-κB signaling.en
dc.typeArticleen
dc.contributor.departmentSystems-oriented Immunology and Inflammation Research, Helmholtz Center for Infection Research, Braunschweig, 38124, Germany. ingo.schmitz@helmholtz-hzi.de.en_GB
dc.identifier.journalCell communication and signaling : CCSen_GB

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