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Comparative distribution of protein components of the A20 ubiquitin-editing complex in normal human brain.

TitleComparative distribution of protein components of the A20 ubiquitin-editing complex in normal human brain.
Publication TypeJournal Article
Year of Publication2012
AuthorsPranski EL, Van Sanford CD, Dalal NV, Orr AL, Karmali D, Cooper DS, Costa N, Heilman CJ, Gearing M, Lah JJ, Levey AI, Betarbet RS
JournalNeurosci Lett
Volume520
Issue1
Pagination104-9
Date Published2012 Jun 27
ISSN1872-7972
KeywordsBrain, Carrier Proteins, DNA-Binding Proteins, Humans, Intracellular Signaling Peptides and Proteins, Neurons, Nuclear Proteins, Repressor Proteins, RNA, Messenger, TNF Receptor-Associated Factor 6, Tumor Necrosis Factor alpha-Induced Protein 3, Ubiquitin, Ubiquitin-Protein Ligases
Abstract

Activation of innate and adaptive immune responses is tightly regulated, as insufficient activation could result in defective clearance of pathogens, while excessive activation might lead to lethal systemic inflammation or autoimmunity. A20 functions as a negative regulator of innate and adaptive immunity by inhibiting NF-κB activation. A20 mediates its inhibitory function in a complex with other proteins including RNF11 and Itch, both E3 ubiquitin ligases and TAX1BP1, an adaptor protein. Since NF-κB has been strongly implicated in various neuronal functions, we predict that its inhibitor, the A20 complex, is also present in the nervous system. In efforts to better understand the role of A20 complex and NF-κB signaling pathway, we determined regional distribution of A20 mRNA as well as protein expression levels and distribution of RNF11, TAX1BP1 and Itch, in different brain regions. The distribution of TRAF6 was also investigated since TRAF6, also an E3 ligase, has an important role in NF-κB signaling pathway. Our investigations, for the first time, describe and demonstrate that the essential components of the A20 ubiquitin-editing complex are present and mainly expressed in neurons. The A20 complex components are also differentially expressed throughout the human brain. This study provides useful information about region specific expression of the A20 complex components that will be invaluable while determining the role of NF-κB signaling pathway in neuronal development and degeneration.

DOI10.1016/j.neulet.2012.05.043
Alternate JournalNeurosci. Lett.
PubMed ID22634524
PubMed Central IDPMC3375179
Grant ListR01 ES015777 / ES / NIEHS NIH HHS / United States
ES012870 / ES / NIEHS NIH HHS / United States
T32 ES012870 / ES / NIEHS NIH HHS / United States
ES015777 / ES / NIEHS NIH HHS / United States
AG025688 / AG / NIA NIH HHS / United States
P50 AG025688 / AG / NIA NIH HHS / United States
T32 NS007480 / NS / NINDS NIH HHS / United States
NS007480 / NS / NINDS NIH HHS / United States