Monarch-1 suppresses non-canonical NF-kappaB activation and p52-dependent chemokine expression in monocytes.
CATERPILLER (NOD, NBD-LRR) proteins are rapidly emerging as important mediators of innate and adaptive immunity. Among these, Monarch-1 operates as a novel attenuating factor of inflammation by suppressing inflammatory responses in activated monocytes. However, the molecular mechanisms by which Monarch-1 performs this important function are not well understood. In this report, we show that Monarch-1 inhibits CD40-mediated activation of NF-kappaB via the non-canonical pathway in human monocytes. This inhibition stems from the ability of Monarch-1 to associate with and induce proteasome-mediated degradation of NF-kappaB inducing kinase. Congruently, silencing Monarch-1 with shRNA enhances the expression of p52-dependent chemokines.
Lich
John D
JD
Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Williams
Kristi L
KL
Moore
Chris B
CB
Arthur
Janelle C
JC
Davis
Beckley K
BK
Taxman
Debra J
DJ
Ting
Jenny P-Y
JP
D019013:CD40 Antigens / Q000037:antagonists & inhibitors / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis*; D006801:Humans; D007249:Inflammation; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D052003:NF-kappa B p52 Subunit / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
D019013:CD40 Antigens; D018925:Chemokines; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases; D000097782:NF-kappaB-Inducing Kinase; C476731:NLRP12 protein, human