Comparative distribution of protein components of the A20 ubiquitin-editing complex in normal human brain.
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.
Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, United States. epransk@emory.edu
Elaine L
EL
Pranski
Carson D
CD
Van Sanford
Nirjari V
NV
Dalal
Adam L
AL
Orr
Dipan
D
Karmali
Deborah S
DS
Cooper
Nichole
N
Costa
Craig J
CJ
Heilman
Marla
M
Gearing
James J
JJ
Lah
Allan I
AI
Levey
Ranjita S
RS
Betarbet
D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C404508:RNF11 protein, human; D012097:Repressor Proteins; D048029:TNF Receptor-Associated Factor 6; D025801:Ubiquitin; C432966:ITCH protein, human; D044767:Ubiquitin-Protein Ligases; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3