Noncanonical NF-κB Signaling in Health and Disease

Gökhan Cildir; Kee Chung Low; Vinay Tergaonkar

doi:10.1016/j.molmed.2016.03.002

Noncanonical NF-κB Signaling in Health and Disease

Trends Mol Med. 2016 May;22(5):414-429. doi: 10.1016/j.molmed.2016.03.002. Epub 2016 Apr 7.

Authors

Gökhan Cildir¹, Kee Chung Low², Vinay Tergaonkar³

Affiliations

¹ Laboratory of NF-κB Signaling, Institute of Molecular and Cell Biology (IMCB), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore 117597, Singapore.
² Laboratory of NF-κB Signaling, Institute of Molecular and Cell Biology (IMCB), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
³ Laboratory of NF-κB Signaling, Institute of Molecular and Cell Biology (IMCB), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore 117597, Singapore; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia. Electronic address: vinayt@imcb.a-star.edu.sg.

PMID: 27068135
DOI: 10.1016/j.molmed.2016.03.002

Abstract

Noncanonical NF-κB signaling differs from canonical NF-κB signaling by being activated through different cell surface receptors, cytoplasmic adaptors, and NF-κB dimers. Under normal physiological conditions, this noncanonical pathway has been implicated in diverse biological processes, including lymphoid organogenesis, B cell maturation, osteoclast differentiation, and various functions of other immune cells. Recently, dysfunction of this pathway has also been causally associated with numerous immune-mediated pathologies and human malignancies. Here, we summarize the core elements as well as the recently identified novel regulators of the noncanonical NF-κB signaling pathway. The involvement of this pathway in different pathologies and the potential therapeutic options that are currently envisaged are also discussed.

Keywords: NIK; non-canonical NF-κB signaling; p52/RelB.

Publication types

Review

MeSH terms

Animals
Cell Line
Disease Models, Animal
Humans
Immune System / cytology
Immune System / metabolism*
Immune System Diseases / immunology
Immune System Diseases / metabolism*
Mice
NF-kappa B / genetics
NF-kappa B / immunology
NF-kappa B / metabolism
Neoplasms / drug therapy
Neoplasms / metabolism*
Protein Binding
Signal Transduction* / genetics

Substances

NF-kappa B