A20-mediated negative regulation of canonical NF-κB signaling pathway

Rajeshree Pujari, Richard Hunte, Wasif N. Khan, Noula Shembade

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

The nuclear factor kappa B (NF-κB) plays vital role in the immune system by regulating innate and adaptive immunity, development and survival of lymphocytes, and lymphoid organogenesis. All known NF-κB activators converge on the IkappaB kinase (IKK) complex to activate the canonical and non-canonical NF-κB pathways the IKK complex contains two catalytic subunits (IKKα and IKKβ) and a regulatory subunit NEMO/IKKγ that regulates the canonical NF-κB pathway, whereas IKKα regulates the non-canonical pathway the process of IKKα activation and its role in the regulation of canonical NF-κB activation remain elusive the canonical pathway is rapidly activated and produces a potent inflammatory response to bacterial and viral infections as well as different types of stress; however, uncontrolled NF-κB activation can lead to autoimmune diseases and cancers therefore, to keep the inflammatory response in check, elaborate negative regulatory mechanisms operate to terminate NF-κB activation at multiple levels by de novo synthesis of NF-κB inhibitory proteins, and orchestration of protein ubiquitination and deubiquitination the NF-κB target genes, IκBα and A20, play critical roles in termination of the active canonical NF-κB pathway. In this review, we discuss our recent findings describing a novel function for IKKα in nucleating the ubiquitin-editing enzyme A20 complex, a major negative regulator of canonical NF-κB signaling. Consistently with an inhibitory function of IKKα, it is targeted by the human T-cell leukemia virus 1 (HTLV-1) oncoprotein, Tax, to prevent assembly of the A20 complex to maintain persistent NF-κB activation that promotes transformation and survival of virus-transformed cells.

Original languageEnglish (US)
Pages (from-to)166-171
Number of pages6
JournalImmunologic Research
Volume57
Issue number1-3
DOIs
StatePublished - Dec 1 2013

Keywords

  • Autoimmunity
  • IKK
  • Innate immunity
  • Ubiquitin NF-κB

ASJC Scopus subject areas

  • Immunology

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